This Article Full Text Full Text (PDF) Supplement All Versions of this Article: biophysj.106.084236v1 92/4/1150    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Coluzza, I. Articles by Frenkel, D. Search for Related Content PubMed PubMed Citation Articles by Coluzza, I. Articles by Frenkel, D.

Monte Carlo Study of Substrate-Induced Folding and Refolding of Lattice Proteins

Ivan Coluzza ^* and Daan Frenkel 

^* Department of Chemistry, Cambridge University Centre for Computational Chemistry, Cambridge, United Kingdom; and Computational Physics, FOM Institute for Atomic and Molecular Physics, Amsterdam, The Netherlands

Correspondence: Address reprint requests to Ivan Coluzza, Cambridge University Centre for Computational Chemistry, Dept. of Chemistry, Lensfield Rd., Cambridge CB2 1EW, UK. Tel: 44-1223-336377; Fax: 44-1223-336362; E-mail: ic247{at}cam.ac.uk.

Many proteins can switch from one conformation to another under the influence of an external driving force, such as the binding to a specific substrate. Using a simple lattice model we show that it is feasible to design protein-like lattice proteins that can have two different conformations, depending on whether or not they are bound to a substrate. We give three different examples of such substrate-induced refolding. In addition, we have explored substrate-induced folding of lattice proteins that do not fold when free in solution. We show that such proteins can bind with the same high specificity as prefolded protein, but have a considerably lower binding free energy. In this way proteins can bind to a substrate in a way that is highly specific, yet reversible.