The Folding Thermodynamics and Kinetics of Crambin Using an All-Atom Monte Carlo Simulation

dc.creatorShimada, J.
dc.creatorKussell, E. L.
dc.creatorShakhnovich, E. I.
dc.date2000-11-22
dc.date.accessioned2026-07-07T02:39:24Z
dc.date.available2026-07-07T02:39:24Z
dc.descriptionWe present a novel Monte Carlo simulation of protein folding, in which all heavy atoms are represented as interacting hard spheres. This model includes all degrees of freedom relevant to folding - all sidechain and backbone torsions - and uses a Go potential. In this study, we focus on the 46 residue alpha-beta protein crambin and two of its structural components, the helix and helix hairpin. For a wide range of temperatures, we have recorded multiple folding events of these three structures from random coils to native conformations that differ by less than 1 A dRMS from their crystal structure coordinates. The thermodynamics and kinetic mechanism of the helix-coil transition obtained from our simulation shows excellent agreement with currently available experimental and molecular dynamics data. Based on insights obtained from folding its smaller structural components, a possible folding mechanism for crambin is proposed. We observe that the folding occurs via a cooperative, first order-like process, and that many folding pathways to the native state exist. One particular sequence of events constitutes a ``fast-folding'' pathway where kinetic traps are avoided. At very low temperatures, a kinetic trap arising from the incorrect packing of sidechains was observed. These results demonstrate that folding to the native state can be observed in a reasonable amount of time on desktop computers even when an all-atom representation is used, provided the energetics sufficiently stabilize the native state.
dc.description43 pages (including figures), 9 figures, submitted to Journal of Molecular Biology
dc.identifierhttps://arxiv.org/abs/cond-mat/0011369
dc.identifierhttp://arxiv.org/abs/cond-mat/0011369
dc.identifier.urihttp://salesiana.dossiersoluciones.com/handle/123456789/17045
dc.subjectSoft Condensed Matter
dc.subjectQuantitative Biology
dc.titleThe Folding Thermodynamics and Kinetics of Crambin Using an All-Atom Monte Carlo Simulation
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