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Title: Substrate Binding Induces Conformational Changes in a Class A β-lactamase That Prime It for Catalysis

Abstract

The emergence and dissemination of bacterial resistance to β-lactam antibiotics via β-lactamase enzymes is a serious problem in clinical settings, often leaving few treatment options for infections resulting from multidrug-resistant superbugs. Understanding the catalytic mechanism of β-lactamases is important for developing strategies to overcome resistance. Binding of a substrate in the active site of an enzyme can alter the conformations and pKas of catalytic residues, thereby contributing to enzyme catalysis. Here we report X-ray and neutron crystal structures of the class A Toho-1 β-lactamase in the apo form and an X-ray structure of a Michaelis-like complex with the cephalosporin antibiotic cefotaxime in the active site. Comparison of these structures reveals that substrate binding induces a series of changes. The side chains of conserved residues important in catalysis, Lys73 and Tyr105, and the main chain of Ser130 alter their conformations, with Nζ of Lys73 moving closer to the position of the conserved catalytic nucleophile Ser70. This movement of Lys73 closer to Ser70 is consistent with proton transfer between the two residues prior to acylation. In combination with the tightly bound catalytic water molecule located between Glu166 and the position of Ser70, the enzyme is primed for catalysis when Ser70 is activatedmore » for nucleophilic attack of the β-lactam ring. Quantum mechanical/molecular mechanical (QM/MM) free energy simulations of models of the wild-type enzyme show that proton transfer from the Nζ of Lys73 to the Oε2 atom of Glu166 is more thermodynamically favorable than when it is absent. Taken together, our findings indicate that substrate binding enhances the favorability of the initial proton transfer steps that precede the formation of the acyl-enzyme intermediate.« less

Authors:
ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [2]; ORCiD logo [1];  [3]; ORCiD logo [4]; ORCiD logo [1]
+ Show Author Affiliations
  1. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
  2. Univ. of Tennessee, Knoxville, TN (United States)
  3. Argonne National Lab. (ANL), Argonne, IL (United States); Univ. at Buffalo, Buffalo, NY (United States)
  4. Univ. of Tennessee, Knoxville, TN (United States); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Publication Date:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER); USDOE Office of Science (SC), Basic Energy Sciences (BES); National Science Foundation (NSF)
OSTI Identifier:
1459304
Alternate Identifier(s):
OSTI ID: 1485285
Grant/Contract Number:  
AC05-00OR22725; AC02-06CH11357
Resource Type:
Accepted Manuscript
Journal Name:
ACS Catalysis
Additional Journal Information:
Journal Volume: 8; Journal Issue: 3; Journal ID: ISSN 2155-5435
Publisher:
American Chemical Society (ACS)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; antibiotic resistance; antibiotics; crystallography; enzyme; enzyme structure; simulation

Citation Formats

Langan, Patricia S., Vandavasi, Venu Gopal, Cooper, Sarah J., Weiss, Kevin L., Ginell, Stephan L., Parks, Jerry M., and Coates, Leighton. Substrate Binding Induces Conformational Changes in a Class A β-lactamase That Prime It for Catalysis. United States: N. p., 2018. Web. doi:10.1021/acscatal.7b04114.
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Langan, Patricia S., Vandavasi, Venu Gopal, Cooper, Sarah J., Weiss, Kevin L., Ginell, Stephan L., Parks, Jerry M., & Coates, Leighton. Substrate Binding Induces Conformational Changes in a Class A β-lactamase That Prime It for Catalysis. United States. https://doi.org/10.1021/acscatal.7b04114
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Langan, Patricia S., Vandavasi, Venu Gopal, Cooper, Sarah J., Weiss, Kevin L., Ginell, Stephan L., Parks, Jerry M., and Coates, Leighton. Thu . "Substrate Binding Induces Conformational Changes in a Class A β-lactamase That Prime It for Catalysis". United States. https://doi.org/10.1021/acscatal.7b04114. https://www.osti.gov/servlets/purl/1459304.
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@article{osti_1459304,
title = {Substrate Binding Induces Conformational Changes in a Class A β-lactamase That Prime It for Catalysis},
author = {Langan, Patricia S. and Vandavasi, Venu Gopal and Cooper, Sarah J. and Weiss, Kevin L. and Ginell, Stephan L. and Parks, Jerry M. and Coates, Leighton},
abstractNote = {The emergence and dissemination of bacterial resistance to β-lactam antibiotics via β-lactamase enzymes is a serious problem in clinical settings, often leaving few treatment options for infections resulting from multidrug-resistant superbugs. Understanding the catalytic mechanism of β-lactamases is important for developing strategies to overcome resistance. Binding of a substrate in the active site of an enzyme can alter the conformations and pKas of catalytic residues, thereby contributing to enzyme catalysis. Here we report X-ray and neutron crystal structures of the class A Toho-1 β-lactamase in the apo form and an X-ray structure of a Michaelis-like complex with the cephalosporin antibiotic cefotaxime in the active site. Comparison of these structures reveals that substrate binding induces a series of changes. The side chains of conserved residues important in catalysis, Lys73 and Tyr105, and the main chain of Ser130 alter their conformations, with Nζ of Lys73 moving closer to the position of the conserved catalytic nucleophile Ser70. This movement of Lys73 closer to Ser70 is consistent with proton transfer between the two residues prior to acylation. In combination with the tightly bound catalytic water molecule located between Glu166 and the position of Ser70, the enzyme is primed for catalysis when Ser70 is activated for nucleophilic attack of the β-lactam ring. Quantum mechanical/molecular mechanical (QM/MM) free energy simulations of models of the wild-type enzyme show that proton transfer from the Nζ of Lys73 to the Oε2 atom of Glu166 is more thermodynamically favorable than when it is absent. Taken together, our findings indicate that substrate binding enhances the favorability of the initial proton transfer steps that precede the formation of the acyl-enzyme intermediate.},
doi = {10.1021/acscatal.7b04114},
journal = {ACS Catalysis},
number = 3,
volume = 8,
place = {United States},
year = {Thu Feb 15 00:00:00 EST 2018},
month = {Thu Feb 15 00:00:00 EST 2018}
}
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Journal Article:
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https://doi.org/10.1021/acscatal.7b04114
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Cited by: 21 works
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Figures / Tables:

Figure 1 Figure 1: Catalytic mechanism of class A β-lactamase inactivation of a β-lactam substrate. A serine nucleophile cleaves the β-lactam bond of the substrate in two steps, acylation and deacylation, which lead to hydrolysis: First, the pre-covalent enzyme-substrate complex is formed and the acylation reaction is initiated (1). General base-catalyzed nucleophilicmore » attack on the β-lactam carbonyl by the serine hydroxy group proceeds through a tetrahedral intermediate (2) and forms a transient acyl-enzyme adduct (3). The acyl-enzyme adduct (3) undergoes general base-catalyzed attack by the hydrolytic water molecule and forms a second tetrahedral intermediate during deacylation (4), which subsequently collapses to form a post-covalent complex (5) prior to release of the hydrolyzed product.« less
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Works referenced in this record:

Penicillin as a Chemotherapeutic Agent
journal, August 1940

Foreword
journal, July 1988

A Brief History of the Antibiotic Era: Lessons Learned and Challenges for the Future
journal, January 2010

Three Decades of  -Lactamase Inhibitors
journal, January 2010

  • Drawz, S. M.; Bonomo, R. A.
  • Clinical Microbiology Reviews, Vol. 23, Issue 1
  • DOI: 10.1128/CMR.00037-09

Origins and Evolution of Antibiotic Resistance
journal, August 2010

  • Davies, J.; Davies, D.
  • Microbiology and Molecular Biology Reviews, Vol. 74, Issue 3
  • DOI: 10.1128/MMBR.00016-10

What's new in antibiotic resistance? Focus on beta-lactamases
journal, June 2006

A standard numbering scheme for the class A β-lactamases
journal, May 1991

  • Ambler, R. P.; Coulson, A. F. W.; Frère, J. M.
  • Biochemical Journal, Vol. 276, Issue 1
  • DOI: 10.1042/bj2760269

A functional classification scheme for beta-lactamases and its correlation with molecular structure
journal, June 1995

  • Bush, K.; Jacoby, G. A.; Medeiros, A. A.
  • Antimicrobial Agents and Chemotherapy, Vol. 39, Issue 6
  • DOI: 10.1128/AAC.39.6.1211

Metallo- -Lactamases: the Quiet before the Storm?
journal, April 2005

The β-lactamase cycle: a tale of selective pressure and bacterial ingenuity
journal, January 1999

  • Matagne, André; Dubus, Alain; Galleni, Moreno
  • Natural Product Reports, Vol. 16, Issue 1
  • DOI: 10.1039/a705983c

Growing Group of Extended-Spectrum  -Lactamases: the CTX-M Enzymes
journal, December 2003

Extended-spectrum and inhibitor-resistant TEM-type beta-lactamases: mutations, specificity, and three-dimensional structure
journal, December 1995

Catalytic properties of class A β-lactamases: efficiency and diversity
journal, March 1998

  • Matagne, André; Lamotte-Brasseur, Josette; FrÈRe, Jean-Marie
  • Biochemical Journal, Vol. 330, Issue 2
  • DOI: 10.1042/bj3300581

CTX-M-type β-lactamases: an emerging group of extended-spectrum enzymes
journal, March 2000

  • Tzouvelekis, L. S.; Tzelepi, E.; Tassios, P. T.
  • International Journal of Antimicrobial Agents, Vol. 14, Issue 2
  • DOI: 10.1016/S0924-8579(99)00165-X

TEM- and SHV-derived extended-spectrum β-lactamases: relationship between selection, structure and function
journal, January 1995

  • Bois, S. K. Du; Marriott, M. S.; Amyes, S. G. B.
  • Journal of Antimicrobial Chemotherapy, Vol. 35, Issue 1
  • DOI: 10.1093/jac/35.1.7

Crystal structure of the E166A mutant of extended-spectrum β-lactamase toho-1 at 1.8 Å resolution 1 1Edited by R. Huber
journal, February 1999

  • Ibuka, Akiko; Taguchi, Ayako; Ishiguro, Masaji
  • Journal of Molecular Biology, Vol. 285, Issue 5
  • DOI: 10.1006/jmbi.1998.2432

Acyl-intermediate Structures of the Extended-spectrum Class A β-Lactamase, Toho-1, in Complex with Cefotaxime, Cephalothin, and Benzylpenicillin
journal, September 2002

  • Shimamura, Tatsuro; Ibuka, Akiko; Fushinobu, Shinya
  • Journal of Biological Chemistry, Vol. 277, Issue 48
  • DOI: 10.1074/jbc.M207884200

Cloning and sequence of the gene encoding a cefotaxime-hydrolyzing class A beta-lactamase isolated from Escherichia coli
journal, October 1995

  • Ishii, Y.; Ohno, A.; Taguchi, H.
  • Antimicrobial Agents and Chemotherapy, Vol. 39, Issue 10
  • DOI: 10.1128/AAC.39.10.2269

Molecular structure of the acyl-enzyme intermediate in β-lactam hydrolysis at 1.7 Å resolution
journal, October 1992

  • Strynadka, Natalie C. J.; Adachi, Hiroyuki; Jensen, Susan E.
  • Nature, Vol. 359, Issue 6397
  • DOI: 10.1038/359700a0

An Ultrahigh Resolution Structure of TEM-1 β-Lactamase Suggests a Role for Glu166 as the General Base in Acylation
journal, May 2002

  • Minasov, George; Wang, Xiaojun; Shoichet, Brian K.
  • Journal of the American Chemical Society, Vol. 124, Issue 19
  • DOI: 10.1021/ja0259640

Ultrahigh Resolution Structure of a Class A β-Lactamase: On the Mechanism and Specificity of the Extended-spectrum SHV-2 Enzyme
journal, April 2003

Site-Directed Mutagenesis of Glutamate-166 in .beta.-Lactamase Leads to a Branched Path Mechanism
journal, June 1994

  • Escobar, Walter A.; Tan, Anthony K.; Lewis, Evan R.
  • Biochemistry, Vol. 33, Issue 24
  • DOI: 10.1021/bi00190a015

The Importance of a Critical Protonation State and the Fate of the Catalytic Steps in Class A β-Lactamases and Penicillin-binding Proteins
journal, May 2004

  • Golemi-Kotra, Dasantila; Meroueh, Samy O.; Kim, Choonkeun
  • Journal of Biological Chemistry, Vol. 279, Issue 33
  • DOI: 10.1074/jbc.M313143200

Lysine-73 Is Involved in the Acylation and Deacylation of β-Lactamase †
journal, May 2000

  • Lietz, Eric J.; Truher, Heather; Kahn, Debra
  • Biochemistry, Vol. 39, Issue 17
  • DOI: 10.1021/bi992681k

Site-directed Mutagenesis of Glutamate 166 in Two β-Lactamases: KINETIC AND MOLECULAR MODELING STUDIES
journal, February 1997

  • Guillaume, Gilliane; Vanhove, Marc; Lamotte-Brasseur, Josette
  • Journal of Biological Chemistry, Vol. 272, Issue 9
  • DOI: 10.1074/jbc.272.9.5438

Neutron and X-ray Crystal Structures of a Perdeuterated Enzyme Inhibitor Complex Reveal the Catalytic Proton Network of the Toho-1 β-Lactamase for the Acylation Reaction
journal, December 2012

  • Tomanicek, Stephen J.; Standaert, Robert F.; Weiss, Kevin L.
  • Journal of Biological Chemistry, Vol. 288, Issue 7
  • DOI: 10.1074/jbc.M112.436238

Exploring the Mechanism of β-Lactam Ring Protonation in the Class A β-lactamase Acylation Mechanism Using Neutron and X-ray Crystallography
journal, December 2015

  • Vandavasi, Venu Gopal; Weiss, Kevin L.; Cooper, Jonathan B.
  • Journal of Medicinal Chemistry, Vol. 59, Issue 1
  • DOI: 10.1021/acs.jmedchem.5b01215

Active-Site Protonation States in an Acyl-Enzyme Intermediate of a Class A β-Lactamase with a Monobactam Substrate
journal, October 2016

  • Vandavasi, Venu Gopal; Langan, Patricia S.; Weiss, Kevin L.
  • Antimicrobial Agents and Chemotherapy, Vol. 61, Issue 1
  • DOI: 10.1128/AAC.01636-16

Toward the Accurate Modeling of DNA: The Importance of Long-Range Electrostatics
journal, May 1995

  • York, Darrin M.; Yang, Weitao; Lee, Hsing
  • Journal of the American Chemical Society, Vol. 117, Issue 17
  • DOI: 10.1021/ja00122a034

Periodic Boundary Conditions in QM/MM Calculations: Implementation and Tests
journal, July 2016

  • Vasilevskaya, Tatiana; Thiel, Walter
  • Journal of Chemical Theory and Computation, Vol. 12, Issue 8
  • DOI: 10.1021/acs.jctc.6b00269

Combined Quantum Mechanics/Molecular Mechanics (QM/MM) Methods in Computational Enzymology
journal, April 2013

  • van der Kamp, Marc W.; Mulholland, Adrian J.
  • Biochemistry, Vol. 52, Issue 16
  • DOI: 10.1021/bi400215w

Identification of Glu166 as the General Base in the Acylation Reaction of Class A β-Lactamases through QM/MM Modeling
journal, August 2003

  • Hermann, Johannes C.; Ridder, Lars; Mulholland, Adrian J.
  • Journal of the American Chemical Society, Vol. 125, Issue 32
  • DOI: 10.1021/ja034434g

Mechanisms of Antibiotic Resistance:  QM/MM Modeling of the Acylation Reaction of a Class A β-Lactamase with Benzylpenicillin
journal, March 2005

  • Hermann, Johannes C.; Hensen, Christian; Ridder, Lars
  • Journal of the American Chemical Society, Vol. 127, Issue 12
  • DOI: 10.1021/ja044210d

Ab Initio QM/MM Study of Class A β-Lactamase Acylation:  Dual Participation of Glu166 and Lys73 in a Concerted Base Promotion of Ser70
journal, November 2005

  • Meroueh, Samy O.; Fisher, Jed F.; Schlegel, H. Bernhard
  • Journal of the American Chemical Society, Vol. 127, Issue 44
  • DOI: 10.1021/ja051592u

High Level QM/MM Modeling of the Formation of the Tetrahedral Intermediate in the Acylation of Wild Type and K73A Mutant TEM-1 Class A β-Lactamase
journal, September 2009

  • Hermann, Johannes C.; Pradon, Juliette; Harvey, Jeremy N.
  • The Journal of Physical Chemistry A, Vol. 113, Issue 43
  • DOI: 10.1021/jp9037254

Molecular mechanisms of antibiotic resistance: QM/MM modelling of deacylation in a class A β-lactamase
journal, January 2006

  • Hermann, Johannes C.; Ridder, Lars; Höltje, Hans-Dieter
  • Org. Biomol. Chem., Vol. 4, Issue 2
  • DOI: 10.1039/B512969A

QM/MM simulations as an assay for carbapenemase activity in class A β-lactamases
journal, January 2014

  • Chudyk, Ewa I.; Limb, Michael A. L.; Jones, Charlotte
  • Chem. Commun., Vol. 50, Issue 94
  • DOI: 10.1039/C4CC06495J

Mechanisms of proton relay and product release by Class A β‐lactamase at ultrahigh resolution
journal, November 2017

  • Lewandowski, Eric M.; Lethbridge, Kathryn G.; Sanishvili, Ruslan
  • The FEBS Journal, Vol. 285, Issue 1
  • DOI: 10.1111/febs.14315

Ligand-Induced Proton Transfer and Low-Barrier Hydrogen Bond Revealed by X-ray Crystallography
journal, June 2015

  • Nichols, Derek A.; Hargis, Jacqueline C.; Sanishvili, Ruslan
  • Journal of the American Chemical Society, Vol. 137, Issue 25
  • DOI: 10.1021/jacs.5b00749

The structure of Toho1 β-lactamase in complex with penicillin reveals the role of Tyr105 in substrate recognition
journal, November 2016

  • Langan, Patricia S.; Vandavasi, Venu Gopal; Weiss, Kevin L.
  • FEBS Open Bio, Vol. 6, Issue 12
  • DOI: 10.1002/2211-5463.12132

XDS
journal, January 2010

  • Kabsch, Wolfgang
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2
  • DOI: 10.1107/S0907444909047337

Overview of the CCP 4 suite and current developments
journal, March 2011

  • Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4
  • DOI: 10.1107/S0907444910045749

A short history of SHELX
journal, December 2007

  • Sheldrick, George M.
  • Acta Crystallographica Section A Foundations of Crystallography, Vol. 64, Issue 1, p. 112-122
  • DOI: 10.1107/S0108767307043930

Protein structures by spallation neutron crystallography
journal, April 2008

  • Langan, Paul; Fisher, Zoë; Kovalevsky, Andrii
  • Journal of Synchrotron Radiation, Vol. 15, Issue 3
  • DOI: 10.1107/S0909049508000824

PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010

  • Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
  • DOI: 10.1107/S0907444909052925

Features and development of Coot
journal, March 2010

  • Emsley, P.; Lohkamp, B.; Scott, W. G.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4
  • DOI: 10.1107/S0907444910007493

Improvement of crystal quality by surface mutations of β-lactamase Toho-1
journal, March 2009

  • Shimamura, Tatsuro; Nitanai, Yasushi; Uchiyama, Takuro
  • Acta Crystallographica Section F Structural Biology and Crystallization Communications, Vol. 65, Issue 4
  • DOI: 10.1107/S1744309109008240

The catalytic efficiency (kcat/Km) of the class A β-lactamase Toho-1 correlates with the thermal stability of its catalytic intermediate analog
journal, April 2010

  • Nitanai, Yasushi; Shimamura, Tatsuro; Uchiyama, Takuro
  • Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1804, Issue 4
  • DOI: 10.1016/j.bbapap.2009.10.023

The Catalytic Mechanism of an Aspartic Proteinase Explored with Neutron and X-ray Diffraction
journal, June 2008

  • Coates, Leighton; Tuan, Han-Fang; Tomanicek, Stephen
  • Journal of the American Chemical Society, Vol. 130, Issue 23
  • DOI: 10.1021/ja801269x

The determination of protonation states in proteins
journal, July 2007

  • Ahmed, H. U.; Blakeley, M. P.; Cianci, M.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 63, Issue 8
  • DOI: 10.1107/S0907444907029976

MolProbity : all-atom structure validation for macromolecular crystallography
journal, December 2009

  • Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1
  • DOI: 10.1107/S0907444909042073

Development and testing of a general amber force field
journal, January 2004

  • Wang, Junmei; Wolf, Romain M.; Caldwell, James W.
  • Journal of Computational Chemistry, Vol. 25, Issue 9
  • DOI: 10.1002/jcc.20035

Fast, efficient generation of high-quality atomic charges. AM1-BCC model: I. Method
journal, January 2000

Fast, efficient generation of high-quality atomic charges. AM1-BCC model: II. Parameterization and validation
journal, October 2002

  • Jakalian, Araz; Jack, David B.; Bayly, Christopher I.
  • Journal of Computational Chemistry, Vol. 23, Issue 16
  • DOI: 10.1002/jcc.10128

The implementation of a fast and accurate QM/MM potential method in Amber
journal, January 2008

  • Walker, Ross C.; Crowley, Michael F.; Case, David A.
  • Journal of Computational Chemistry, Vol. 29, Issue 7
  • DOI: 10.1002/jcc.20857

ff14SB: Improving the Accuracy of Protein Side Chain and Backbone Parameters from ff99SB
journal, July 2015

  • Maier, James A.; Martinez, Carmenza; Kasavajhala, Koushik
  • Journal of Chemical Theory and Computation, Vol. 11, Issue 8
  • DOI: 10.1021/acs.jctc.5b00255

Comparison of simple potential functions for simulating liquid water
journal, July 1983

  • Jorgensen, William L.; Chandrasekhar, Jayaraman; Madura, Jeffry D.
  • The Journal of Chemical Physics, Vol. 79, Issue 2
  • DOI: 10.1063/1.445869

Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes
journal, March 1977

  • Ryckaert, Jean-Paul; Ciccotti, Giovanni; Berendsen, Herman J. C.
  • Journal of Computational Physics, Vol. 23, Issue 3
  • DOI: 10.1016/0021-9991(77)90098-5

Settle: An analytical version of the SHAKE and RATTLE algorithm for rigid water models
journal, October 1992

  • Miyamoto, Shuichi; Kollman, Peter A.
  • Journal of Computational Chemistry, Vol. 13, Issue 8
  • DOI: 10.1002/jcc.540130805

Particle mesh Ewald: An N ⋅log( N ) method for Ewald sums in large systems
journal, June 1993

  • Darden, Tom; York, Darrin; Pedersen, Lee
  • The Journal of Chemical Physics, Vol. 98, Issue 12
  • DOI: 10.1063/1.464397

A smooth particle mesh Ewald method
journal, November 1995

  • Essmann, Ulrich; Perera, Lalith; Berkowitz, Max L.
  • The Journal of Chemical Physics, Vol. 103, Issue 19
  • DOI: 10.1063/1.470117

Accuracy of Density Functionals in the Prediction of Electronic Proton Affinities of Amino Acid Side Chains
journal, October 2011

  • Brás, Natércia F.; Perez, Marta A. S.; Fernandes, Pedro A.
  • Journal of Chemical Theory and Computation, Vol. 7, Issue 12
  • DOI: 10.1021/ct200309v

Enzyme mechanisms with hybrid quantum and molecular mechanical potentials. I. Theoretical considerations
journal, January 1996

Optimization of parameters for semiempirical methods V: Modification of NDDO approximations and application to 70 elements
journal, September 2007

Can Semi-empirical Calculations Help Solve Mass Spectrometry Problems? Protonation Sites and Proton Affinities of Amino Acids
journal, August 2013

  • Amorim Madeira, Paulo J.; Vaz, Pedro D.; Bettencourt da Silva, R. J. N.
  • ChemPlusChem, Vol. 78, Issue 9
  • DOI: 10.1002/cplu.201300173

THE weighted histogram analysis method for free-energy calculations on biomolecules. I. The method
journal, October 1992

  • Kumar, Shankar; Rosenberg, John M.; Bouzida, Djamal
  • Journal of Computational Chemistry, Vol. 13, Issue 8
  • DOI: 10.1002/jcc.540130812

The calculation of the potential of mean force using computer simulations
journal, September 1995

Mechanism of acyl transfer by the class A serine β-lactamase of Streptomyces albus G
journal, October 1991

  • Lamotte-Brasseur, J.; Dive, G.; Dideberg, O.
  • Biochemical Journal, Vol. 279, Issue 1
  • DOI: 10.1042/bj2790213

Engineering enzyme specificity by "substrate-assisted catalysis"
journal, July 1987

Structural and Biochemical Evidence That a TEM-1 β-Lactamase N170G Active Site Mutant Acts via Substrate-assisted Catalysis
journal, October 2009

  • Brown, Nicholas G.; Shanker, Sreejesh; Prasad, B. V. Venkataram
  • Journal of Biological Chemistry, Vol. 284, Issue 48
  • DOI: 10.1074/jbc.M109.053819
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