Studying inter-residue interactions provides insight into the folding and stability of both soluble and membrane proteins and is essential for developing computational tools for protein structure prediction. As the first step, various approaches for elucidating such interactions within protein structures have been proposed and proven useful. Since different approaches may grasp different aspects of protein structural folds, it is of interest to systematically compare them. In this work, we applied four approaches for determining inter-residue interactions to the analysis of three distinct structure datasets of helical membrane proteins and compared their correlation to the three individual quality measures of structures in these datasets. These datasets included one of 35 structures of rhodopsin receptors and bacterial rhodopsins determined at various resolutions, one derived from the HOMEP benchmark dataset previously reported, and one comprising of 139 homology models. It was found that the correlation between the average number of inter-residue interactions obtained by applying the four approaches and the available structure quality measures varied quite significantly among them. The best correlation was achieved by the approach focusing exclusively on favorable inter-residue interactions. These results provide interesting insight for the development of objective quality measure for the structure prediction of helical membrane proteins.
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http://dx.doi.org/10.1002/bip.21175 | DOI Listing |
Protein Sci
December 2024
Department of Mechanical Engineering and Materials Science, Yale University, New Haven, Connecticut, USA.
Proteins naturally occur in crowded cellular environments and interact with other proteins, nucleic acids, and organelles. Since most previous experimental protein structure determination techniques require that proteins occur in idealized, non-physiological environments, the effects of realistic cellular environments on protein structure are largely unexplored. Recently, Förster resonance energy transfer (FRET) has been shown to be an effective experimental method for investigating protein structure in vivo.
View Article and Find Full Text PDFPhys Chem Chem Phys
November 2024
Department of Chemical and Biological Sciences, S. N. Bose National Centre for Basic Sciences, JD Block, Sector III, Salt Lake, Kolkata 700106, India.
Acetylcholinesterase (AChE) has emerged as an important drug target for the treatment of neurodegenerative disorders such as Alzheimer's disease (AD). Recent experimental studies indicate that certain antidiabetic drugs can be repurposed as potent AChE inhibitors. Enzymatic kinetic assays suggest that the antidiabetic drug chlorpropamide (CPM) acts as a noncompetitive inhibitor, but the mechanism of action and the binding site(s) of interaction with AChE are not known.
View Article and Find Full Text PDFBioinformatics
November 2024
LAAS-CNRS, Université de Toulouse, CNRS, 31400 Toulouse, France.
Motivation: Characterizing the structure of flexible proteins, particularly within the realm of intrinsic disorder, presents a formidable challenge due to their high conformational variability. Currently, their structural representation relies on (possibly large) conformational ensembles derived from a combination of experimental and computational methods. The detailed structural analysis of these ensembles is a difficult task, for which existing tools have limited effectiveness.
View Article and Find Full Text PDFInt J Mol Sci
September 2024
Anhui Province Key Laboratory of Pollutant Sensitive Materials and Environmental Remediation, College of Life Sciences, Huaibei Normal University, Huaibei 235000, China.
The enantioselective mechanism of the esterase QeH against the two enantiomers of quizalofop-ethyl (QE) has been primitively studied using computational and experimental approaches. However, it is still unclear how the esterase QeH adjusts its conformation to adapt to substrate binding and promote enzymrate interactions and catalytic dynamics were reproduced by performing independent molecular dynamics (MD) runs on the QeH-()/()-QE complexes with a newly developed residue-specific force field (RSFF2C). Our results indicated that the benzene ring of the ()-QE structure can simultaneously form anion-π and cation-π interactions with the side-chain group of Glu328 and Arg384 in the binding cavity of the QeH-()-QE complex, resulting in ()-QE being closer to its catalytic triplet system (Ser78-Lys81-Tyr189) with the distances measured for the hydroxyl oxygen atom of the catalytic Ser78 of QeH and the carbonyl carbon atom of ()-QE of 7.
View Article and Find Full Text PDFJ Phys Chem B
September 2024
Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan.
Within the protein interior, where we observe various types of interactions, nonuniform flow of thermal energy occurs along the polypeptide chain and through nonbonded native contacts, leading to inhomogeneous transport efficiencies from one site to another. The folded native protein serves not merely as thermal transfer medium but, more importantly, as sophisticated molecular nanomachines in cells. Therefore, we are particularly interested in what sort of "communication" is mediated through native contacts in the folded proteins and how such features are quantitatively depicted in terms of local transport coefficients of heat currents.
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