Premium
Monte carlo studies on equilibrium globular protein folding. I. Homopolymeric lattice models of β‐barrel proteins
Author(s) -
Kolinski Andrzej,
Skolnick Jeffrey,
Yaris Robert
Publication year - 1987
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360260613
Subject(s) - cooperativity , globular protein , chemistry , protein folding , native state , monte carlo method , statistical physics , crystallography , lattice protein , equilibrium unfolding , chemical physics , thermodynamics , physics , biochemistry , statistics , mathematics
Dynamic Monte Carlo studies have been performed on various diamond lattice models of β‐proteins. Unlike previous work, no bias toward the native state is introduced; instead, the protein is allowed to freely hunt through all of phase space to find the equilibrium conformation. Thus, these systems may aid in the elucidation of the rules governing protein folding from a given primary sequence; in particular, the interplay of short‐ vs long‐range interaction can be explored. Three distinct models (AC) were examined. In model A, in addition to the preference for trans (t) over gauche states ( g + and g − ) (thereby perhaps favoring β‐sheet formation), attractive interactions are allowed between all nonbonded, nearest neighbor pairs of segments. If the molecules possess a relatively large fraction of t states in the denatured form, on cooling spontaneous collapse to a well‐defined β‐barrel is observed. Unfortunately, in model A the denatured state exhibits too much secondary structure to correctly model the globular protein collapse transition. Thus in models B and C, the local stiffness is reduced. In model B, in the absence of long‐range interactions, t and g states are equally weighted, and cooperativity is introduced by favoring formation of adjacent pairs of nonbonded (but not necessarily parallel) t states. While the denatured state of these systems behaves like a random coil, their native globular structure is poorly defined. Model C retains the cooperativity of model B but allows for a slight preference of t over g states in the short‐range interactions. Here, the denatured state is indistinguishable from a random coil, and the globular state is a well‐defined β‐barrel. Over a range of chain lengths, the collapse is well represented by an all‐or‐none model. Hence, model C possesses the essential qualitative features observed in real globular proteins. These studies strongly suggest that the uniqueness of the globular conformation requires some residual secondary structure to be present in the denatured state.