Conformations of Proteins in Equilibrium.pdf

a r X i v : c o n d - m a t / 0 1 0 7 6 2 4 v 1 [ c o n d - m a t .s t a t - m e c h ] 3 1 J u l 2 0 0 1 Conformations of Proteins in Equilibrium Cristian Micheletti1, Jayanth R. Banavar2 and Amos Maritan1 (1) International School for Advanced Studies (S.I.S.S.A.) and INFM, Via Beirut 2-4, 34014 Trieste, Italy (2) Department of Physics and Center for Materials Physics, 104 Davey Laboratory, The Pennsylvania State University, University Park, Pennsylvania 16802 (February 1, 2008) We introduce a simple theoretical approach for an equilibrium study of proteins with known native state structures. We test our approach with results on well-studied globular proteins, Chymotrypsin Inhibitor (2ci2), Barnase and the alpha spectrin SH3 domain and present evidence for a hierarchical onset of order on lowering the temperature with significant organization at the local level even at high temperatures. A further application to the folding process of HIV-1 protease shows that the model can be reliably used to identify key folding sites that are responsible for the development of drug resistance . Recent experimental and theoretical advances [1] have shown that the topology of the native structure of a protein plays an important role in determining many of its attributes. The number of distinct native state conformations of proteins is limited [2] – often several distinct sequences fold into the same native state structure. The native state structures of proteins contain secondary motifs (helices and sheets) in lower dimensional manifolds which are curled into neat patterns (somewhat analogous to the packing of clothes in a suitcase) and play a central role in the folding process [3–5]. The problem of protein folding entails the study of the non-equilibrium dynamics in a rugged free energy landscape [6]. A valuable starting point for attacking such a problem is through a thorough equilibrium analysis of proteins with known native state structures. This would be useful for th