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Thermodynamic prediction of protein neutrality Jesse D. Bloom*

Summary: Thermodynamic prediction of protein neutrality
Jesse D. Bloom*
, Jonathan J. Silberg§
, Claus O. Wilke¶
, D. Allan Drummond
, Christoph Adami¶
and Frances H. Arnold*
*Division of Chemistry and Chemical Engineering 210-41, Digital Life Laboratory 136-93, and Computation and Neural Systems, California Institute of
Technology, Pasadena, CA 91125; §Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77005; and ¶Keck Graduate Institute,
535 Watson Drive, Claremont, CA 91711
Edited by Alan R. Fersht, University of Cambridge, Cambridge, United Kingdom, and approved December 3, 2004 (received for review September 10, 2004)
We present a simple theory that uses thermodynamic parameters
to predict the probability that a protein retains the wild-type
structure after one or more random amino acid substitutions. Our
theory predicts that for large numbers of substitutions the prob-
ability that a protein retains its structure will decline exponentially
with the number of substitutions, with the severity of this decline
determined by properties of the structure. Our theory also predicts
that a protein can gain extra robustness to the first few substitu-


Source: Arnold, Frances H. - Division of Chemistry and Chemical Engineering, California Institute of Technology


Collections: Chemistry; Biology and Medicine