An All-atom Structure-Based Potential for Proteins: Bridging Minimal Models with All-atom Empirical Forcefields

By P. Whitford, J. Noel, S. Gosavi, Alexander Schug, K. Sanbonmatsu, José N. Onuchic. Proteins: Structure, Function, and Bioinformatics, 2009

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Protein dynamics take place on many time and length scales. Coarse‐grained structure‐based $ {\bf (G{\overline o})} $ models utilize the funneled energy landscape theory of protein folding to provide an understanding of both long time and long length scale dynamics. All‐atom empirical forcefields with explicit solvent can elucidate our understanding of short time dynamics with high energetic and structural resolution. Thus, structure‐based models with atomic details included can be used to bridge our understanding between these two approaches. We report on the robustness of folding mechanisms in one such all‐atom model. Results for the B domain of Protein A, the SH3 domain of C‐Src Kinase, and Chymotrypsin Inhibitor 2 are reported. The interplay between side chain packing and backbone folding is explored. We also compare this model to a Cα structure‐based model and an all‐atom empirical forcefield. Key findings include: (1) backbone collapse is accompanied by partial side chain packing in a cooperative transition and residual side chain packing occurs gradually with decreasing temperature, (2) folding mechanisms are robust to variations of the energetic parameters, (3) protein folding free‐energy barriers can be manipulated through parametric modifications, (4) the global folding mechanisms in a Cα model and the all‐atom model agree, although differences can be attributed to energetic heterogeneity in the all‐atom model, and (5) proline residues have significant effects on folding mechanisms, independent of isomerization effects. Because this structure‐based model has atomic resolution, this work lays the foundation for future studies to probe the contributions of specific energetic factors on protein folding and function. Proteins 2009. © 2008 Wiley‐Liss, Inc.

Subfields: Materials Chemistry, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/63af62473649ed990d8f5cefeca6ebad47ac33d4

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Citations in the corpus

Computational modeling of phosphotransfer complexes in two-component signaling. (2010, methodology): “…force fields, variants using multiwelled Gaussians for the contacts (Lammert et al ., 2009), C a C b (Finke et al ., 2004; Oliveira et al ., 2008) or all-atom representations have been developed (Linhananta and Zhou, 2002; Shimada et al ., 2001; Whitford et al ., 2009a; Zhou et al ., 2003).”
High-resolution protein complexes from integrating genomic information with molecular simulation (2009, background): “Based on the energy-landscape theory (19), SBS coarse grain a protein’s physical/chemical interactions into smoothened effective interactions, providing access to time scales sufficient to simulate (un)folding and large-scale conformational motions (20, 21).”
Structural basis of histidine kinase autophosphorylation deduced by integrating genomics, molecular dynamics, and mutagenesis (2012, background): “interdomain contacts and an interaction between the ATP-Pγ and the conserved His-260 residue as additional Go-type contacts (41, 42) into low-”