Modeling of Disordered Protein Structures Using Monte Carlo Simulations and Knowledge-Based Statistical Force Fields

Abstract

The description of protein disordered states is important for understanding protein folding mechanisms and their functions. In this short review, we briefly describe a simulation approach to modeling protein interactions, which involve disordered peptide partners or intrinsically disordered protein regions, and unfolded states of globular proteins. It is based on the CABS coarse-grained protein model that uses a Monte Carlo (MC) sampling scheme and a knowledge-based statistical force field. We review several case studies showing that description of protein disordered states resulting from CABS simulations is consistent with experimental data. The case studies comprise investigations of protein–peptide binding and protein folding processes. The CABS model has been recently made available as the simulation engine of multiscale modeling tools enabling studies of protein–peptide docking and protein flexibility. Those tools offer customization of the modeling process, driving the conformational search using distance restraints, reconstruction of selected models to all-atom resolution, and simulation of large protein systems in a reasonable computational time. Therefore, CABS can be combined in integrative modeling pipelines incorporating experimental data and other modeling tools of various resolution.

Features of molecular recognition of intrinsically disordered proteins via coupled folding and binding

“…2,3,[71][72][73][74][75] In parallel, molecular modeling and computer simulations provide atomic pictures of conformation ensembles and binding processes as well as reveal important underlying physical principles. [76][77][78][79][80][81][82] 3 | RATE CONSTANTS Coupled folding with binding has been suggested to enhance the binding rates of IDPs/IDRs. 83 Theoretical analysis and computer simulations predicted that the "fly-casting" effect accelerates the binding rate by twofolds to threefolds.…”

Protocols for fast simulations of protein structure flexibility using CABS-flex and SURPASS

“…Modifications of these options may have some practical effects on the simulation outcome. The simulation length and number of models in the output trajectory are controlled by the values assigned to the set of --mc options (-y, -s, -a) (detailed description of the sampling procedure that is controlled by these options has been recently provided in the review by Ciemny et al [24]). Using the -t option, user allows setting up the CABS simulation temperatures: at the beginning of the simulation (TINIT) and at the end of simulation (TFINAL).…”

Recent Advances in Coarse-Grained Models for Biomolecules and Their Applications

“…The force field used is based upon several potentials of the mean force obtained from the calculated structural correlations of solved protein structures. It has been successfully applied for the simulation studies of protein folding [92][93][94][95].…”