Coarse-grained models for proteins

Tozzini, Valentina

doi:10.1016/j.sbi.2005.02.005

Cited by 775 publications

(648 citation statements)

References 80 publications

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“…Enormous progress has been made in all-atom calculations, due to extensive use of world-distributed computing (20), implementation of all-atom molecular dynamics software on graphical processor units (21), and, most notably, the construction of dedicated machines (22). However, coarsegrained approaches (23)(24)(25), in which several atoms are merged into single interaction sites, are used very extensively, because they enable us to treat protein systems at time and dimensional scales, which are orders of magnitude larger (26) than those possible in all-atom computations. During the past 20 y, we have been developing (27)(28)(29)(30) a simplified model for proteins termed UNRES, in which two interaction sites per residue are defined, namely, a united side chain and a united peptide group.…”

Section: Significancementioning

confidence: 99%

Lessons from application of the UNRES force field to predictions of structures of CASP10 targets

Mozolewska

Krupa

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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The performance of the physics-based protocol, whose main component is the United Residue (UNRES) physics-based coarse-grained force field, developed in our laboratory for the prediction of protein structure from amino acid sequence, is illustrated. Candidate models are selected, based on probabilities of the conformational families determined by multiplexed replica-exchange simulations, from the 10th Community Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction (CASP10). For target T0663, classified as a new fold, which consists of two α + β domains homologous to those of known proteins, UNRES predicted the correct symmetry of packing, in which the domains are rotated with respect to each other by 180°in the experimental structure. By contrast, models obtained by knowledge-based methods, in which each domain is modeled very accurately but not rotated, resulted in incorrect packing. Two UNRES models of this target were featured by the assessors. Correct domain packing was also predicted by UNRES for the homologous target T0644, which has a similar structure to that of T0663, except that the two domains are not rotated. Predictions for two other targets, T0668 and T0684_D2, are among the best ones by global distance test score. These results suggest that our physicsbased method has substantial predictive power. In particular, it has the ability to predict domain-domain orientations, which is a significant advance in the state of the art.protein folding | structure symmetry | multi-domain packing P rediction of protein structures from amino acid sequence still remains an unsolved problem of computational biology. Although, since the famous experiments by Anfinsen (1), it is known that a protein adopts the structure which is the (kinetically reachable) global minimum of the free energy of a system, it is not straightforward to implement this physical principle in practice because of the inaccuracy of existing force fields and because of the enormous difficulty to search the conformational space of the system. Therefore, the most effective methods for protein-structure prediction nowadays are knowledge-based approaches, in which database information is incorporated explicitly into the procedure (2). These methods can be divided into three categories, namely, comparative (homology) modeling (3-5), in which the target sequence is compared with the sequences for which experimental structures are known and those structures are usually selected as candidate models for which the greatest similarity is observed; threading (6-8), in which the target sequence is superposed on structures from a database, and those which give the highest score (lowest pseudoenergy) are selected as candidate predictions; and, finally, the fragment-assembly or minithreading method developed by David Baker and colleagues (9, 10), in which the predicted structure is assembled from nine-residue fragments extracted from a protein-structure database, and knowledge-and physicsbased filters are applied at each asse...

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Section: Significancementioning

confidence: 99%

Lessons from application of the UNRES force field to predictions of structures of CASP10 targets

Mozolewska

Krupa

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…41 and the references therein. We find that the Pearson correlation coefficient is rather low for scheme I, where all-atom local minimum configurations are reoptimized upon local rigidification.…”

Section: Correlation Analysis For the Tryptophan Zippermentioning

confidence: 99%

A Local Rigid Body Framework for Global Optimization of Biomolecules

Kusumaatmaja

Whittleston

Wales

2012

J. Chem. Theory Comput.

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Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-pro t purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. AbstractWe present a local rigid body framework for simulations of biomolecules. In this framework, arbritrary sets of atoms may be treated as rigid bodies. Such groupings reduce the number of degrees of freedom, which can result in a significant reduction of computational time.As benchmarks, we consider global optimization for the tryptophan zipper (trpzip 1, 1LE0; using the CHARMM force field) and chignolin (1UAO; using the AMBER force field). We use a basin-hopping algorithm to find the global minima and compute the mean first encounter time from random starting configurations with and without the local rigid body framework.Minimal groupings are used, where only peptide bonds, termini and side chain rings are considered rigid. Finding the global minimum is 4.2 and 2.5 times faster, respectively, for trpzip 1 and chignolin, within the local rigid body framework. We further compare O(10 5 ) low-lying local minima to the fully relaxed unconstrained representation for trpzip 1 at different levels of rigidification. The resulting Pearson correlation coefficients, and thus the apparent intrinsic rigidity of the various groups, appear in the following order: side chain rings > termini > trigonal planar centres ≥ peptide bonds side chains. This approach is likely to be even more beneficial for structure prediction in larger biomolecules.

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“…Coarse-grained (CG) models for biomolecules (Saunders and Voth 2013;Takada 2012;Tozzini 2005) have been used to investigate the behavior of large biomolecules. In the CG models, the biomolecule is modeled with a particle that represents a sum of several atoms.…”

Section: Future Perspective Of Enhanced Sampling Methodsmentioning

confidence: 99%

Enhanced sampling simulations to construct free-energy landscape of protein–partner substrate interaction

2016

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Molecular dynamics (MD) simulations using allatom and explicit solvent models provide valuable information on the detailed behavior of protein-partner substrate binding at the atomic level. As the power of computational resources increase, MD simulations are being used more widely and easily. However, it is still difficult to investigate the thermodynamic properties of protein-partner substrate binding and protein folding with conventional MD simulations. Enhanced sampling methods have been developed to sample conformations that reflect equilibrium conditions in a more efficient manner than conventional MD simulations, thereby allowing the construction of accurate free-energy landscapes. In this review, we discuss these enhanced sampling methods using a series of case-by-case examples. In particular, we review enhanced sampling methods conforming to trivial trajectory parallelization, virtual-system coupled multicanonical MD, and adaptive lambda square dynamics. These methods have been recently developed based on the existing method of multicanonical MD simulation. Their applications are reviewed with an emphasis on describing their practical implementation. In our concluding remarks we explore extensions of the enhanced sampling methods that may allow for even more efficient sampling.

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Coarse-grained models for proteins

Cited by 775 publications

References 80 publications

Lessons from application of the UNRES force field to predictions of structures of CASP10 targets

Lessons from application of the UNRES force field to predictions of structures of CASP10 targets

A Local Rigid Body Framework for Global Optimization of Biomolecules

Enhanced sampling simulations to construct free-energy landscape of protein–partner substrate interaction

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