The relative distance and orientation in contacting residue pairs plays a significant role in protein folding and stabilization. We hereby devise a new knowledge-based, coarse-grained contact potential, so-called ICOSA, by correlating inter-residue contact distance and orientation in evaluating pair-wise inter-residue interactions. The rationale of our approach is to establish icosahedral local coordinates to estimate the statistical residue contact distributions in all spherical triangular shells within a sphere. We extend the theory of finite ideal gas reference state to icosahedral local coordinates. ICOSA incorporates long-range contact interactions, which is critical to ICOSA sensitivity and is justified in statistical rigor. With only backbone atoms information, ICOSA is at least comparable to all-atom, fine-grained potentials such as Rosetta, DFIRE, I-TASSER, and OPUS in discriminating near-natives from misfold protein conformations in the Rosetta and I-TASSER protein decoy sets. ICOSA also outperforms a set of widely used coarse-grained potentials and is comparable to all-atom, fine-grained potentials in identifying CASP10 models.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.jmb.2015.05.022 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Molecular-Scale Simulation of Wetting of Actin Filaments by Protein Droplets.
J Phys Chem B
January 2025
Department of Computer and Information Sciences, Department of Materials Science and Engineering, University of Delaware, Newark, Delaware 19716, United States.
Liquid phase-separating proteins can form condensates that play an important role in spatial and temporal organization of biological cells. The understanding of the mechanisms that lead to the formation of protein condensates and their interactions with other biomolecules may lead to processing routes for soft materials with tailored geometry and function. Fused in sarcoma (FUS) is an example of a nuclear protein that forms stable complexes, and recent studies have highlighted its ability to wet actin filaments and bundle them into networks.
View Article and Find Full Text PDFElucidating the structure and function of a membrane-active plant protein domain using in silico mutagenesis.
Biochim Biophys Acta Biomembr
January 2025
Land and Food Systems, University of British Columbia, Vancouver, Canada; Faculty of Agricultural, Life and Environmental Sciences, University of Alberta, Edmonton, Canada. Electronic address:
The Solanum tuberosum (common potato) plant specific insert (StPSI) is an antimicrobial protein domain that exhibits membrane-disrupting and membrane-fusing activity upon dimerization at acidic pH, activity proposed to involve electrostatic attraction and membrane anchoring mediated by specific positively-charged and conserved tryptophan residues, respectively. This study is the first to employ an in silico mutagenesis approach to clarify the structure-function relationship of a plant specific insert (PSI), where ten rationally-mutated StPSI variants were investigated using all-atom and coarse-grained molecular dynamics. The tryptophan (W) residue at position 18 (W18) of wild-type StPSI was predicted to confer structural flexibility to the dimer and mediate a partial separation of the assembled monomers upon bilayer contact, while residues including W77 and the lysine (K) residue at position 83 (K83) were predicted to stabilize secondary structure and influence association with the model membrane.
View Article and Find Full Text PDFNucleosome condensate and linker DNA alter chromatin folding pathways and rates.
bioRxiv
November 2024
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Unlabelled: Chromatin organization is essential for DNA packaging and gene regulation in eukaryotic genomes. While significant progresses have been made, the exact atomistic arrangement of nucleosomes remains controversial. Using a well-calibrated residue-level coarse-grained model and advanced dynamics modeling techniques, particularly the non-Markovian dynamics model, we map the free energy landscape of tetra-nucleosome systems, identify both metastable conformations and intermediate states in folding pathways, and quantify the folding kinetics.
View Article and Find Full Text PDFCoarse-Grained Modeling of the Water/Alkane Wetting and Dewetting Processes on Fluorinated Coatings.
Langmuir
December 2024
Siemens Industry Software Netherlands B.V, The Hague 2595 BN, Netherlands.
This work provides a framework to digitally assess any droplet's static and dynamic contact angles on coatings and polymeric substrates. We are introducing a new dissipative particle dynamics coarse-grained model to attain the spatiotemporal conditions and the coexistence of different phases that such investigation dictates. Two computational techniques are additionally developed; a robust technique to calculate the static contact angle using density profiles and a perturbation method to evaluate dynamic contact angles.
View Article and Find Full Text PDFFluctuating Chromatin Facilitates Enhancer-Promoter Communication by Regulating Transcriptional Clustering Dynamics.
J Phys Chem Lett
November 2024
Advanced Materials Thrust, Function Hub, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou, Guangdong 511400, China.
Enhancers regulate gene expression by forming contacts with distant promoters. Phase-separated condensates or clusters formed by transcription factors (TFs) and cofactors are thought to facilitate these enhancer-promoter (E-P) interactions. Using polymer physics, we developed distinct coarse-grained chromatin models that produce similar ensemble-averaged Hi-C maps but with "stable" and "dynamic" characteristics.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!