Protein Structure Determination Using Protein Threading and Sparse NMR Data

Conference · Sun Nov 14 04:00:00 EST 1999

OSTI ID:14619

Crawford, O H ^[1]; Einstein, J R; Xu, D; Xu, Y

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1. ORNL

It is well known that the NMR method for protein structure determination applies to small proteins and that its effectiveness decreases very rapidly as the molecular weight increases beyond about 30 kD. We have recently developed a method for protein structure determination that can fully utilize partial NMR data as calculation constraints. The core of the method is a threading algorithm that guarantees to find a globally optimal alignment between a query sequence and a template structure, under distance constraints specified by NMR/NOE data. Our preliminary tests have demonstrated that a small number of NMR/NOE distance restraints can significantly improve threading performance in both fold recognition and threading-alignment accuracy, and can possibly extend threading's scope of applicability from structural homologs to structural analogs. An accurate backbone structure generated by NMR-constrained threading can then provide a significant amount of structural information, equivalent to that provided by the NMR method with many NMR/NOE restraints; and hence can greatly reduce the amount of NMR data typically required for accurate structure determination. Our preliminary study suggests that a small number of NMR/NOE restraints may suffice to determine adequately the all-atom structure when those restraints are incorporated in a procedure combining threading, modeling of loops and sidechains, and molecular dynamics simulation. Potentially, this new technique can expand NMR's capability to larger proteins.

• Research Organization: Oak Ridge National Lab., TN (US)
• Sponsoring Organization: USDOE Office of Science (US)
• DOE Contract Number: AC05-96OR22464
• OSTI ID: 14619
• Report Number(s): ORNL/CP-104963
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
ACCURACY
ALGORITHMS
ALIGNMENT
ENERGY MINIMIZATION
FOLD RECOGNITION
MOLECULAR WEIGHT
NMR
NUCLEAR MAGNETIC RESONANCE
PERFORMANCE
PROTEIN STRUCTURE
PROTEIN STRUCTURE DETERMINATION
PROTEIN THREADING
PROTEINS
RESTRAINTS
SIMULATION