98%
921
2 minutes
20
This review focuses on recent work that has begun to establish specific functional roles for protein conformational dynamics, specifically how the conformational landscapes that proteins can sample can evolve under laboratory based evolutionary selection. We discuss recent technical advances in computational and biophysical chemistry, which have provided us with new ways to dissect evolutionary processes. Finally, we offer some perspectives on the emerging view of conformational dynamics and evolution, and the challenges that we face in rationally engineering conformational dynamics.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.sbi.2017.09.005 | DOI Listing |
RSC Adv
September 2025
Departament de Química, Universitat Autònoma de Barcelona Bellaterra 08193 Barcelona Spain
Mammalian ALOX15 are allosteric enzymes but the mechanism of allosteric regulation remains a matter of discussion. Octyl (-(5-(1-indol-2-yl)-2-methoxyphenyl)sulfamoyl)carbamate inhibits the linoleate oxygenase activity of ALOX15 at nanomolar concentrations, but oxygenation of arachidonic acid is hardly affected. The mechanism of substrate selective inhibition suggests inter-monomer communication within the allosteric ALOX15 dimer complex, in which the inhibitor binding to monomer A induces conformational alterations in the structure of the active site of monomer B.
View Article and Find Full Text PDFSAR QSAR Environ Res
August 2025
Center for Medical Artificial Intelligence, Shandong University of Traditional Chinese Medicine, Qingdao, China.
Phosphorylation plays an important role in the activity of CDK2 and inhibitor binding, but the corresponding molecular mechanism is still insufficiently known. To address this gap, the current study innovatively integrates molecular dynamics (MD) simulations, deep learning (DL) techniques, and free energy landscape (FEL) analysis to systematically explore the action mechanisms of two inhibitors (SCH and CYC) when CDK2 is in a phosphorylated state and bound state of CyclinE. With the help of MD trajectory-based DL, key functional domains such as the loops L3 loop and L7 are successfully identified.
View Article and Find Full Text PDFSAR QSAR Environ Res
August 2025
Structural Biology and Biocomputing Lab, Department of Bioinformatics, Alagappa University, Karaikudi, India.
, a causative agent of lymphatic filariasis, relies on its endosymbiont for survival. MurE ligase, a key enzyme in peptidoglycan biosynthesis, serves as a promising drug target for anti-filarial therapy. In this study, we employed a hierarchical virtual screening pipeline to identify phytochemical inhibitors targeting the MurE enzyme of the endosymbiont of (MurE).
View Article and Find Full Text PDFACS Nano
September 2025
Department of Biomedical Engineering, Tufts University, Medford, Massachusetts 02155, United States.
Achieving high performance nanoscale photonic functionalities remains extraordinarily challenging when using naturally derived biomaterials. The ability to manipulate ultrathin films of structural proteins─combined with photolithographic control of their polymorphism─unlocks a compelling route toward engineering biopolymer-based photonic crystals with precisely defined photonic bandgaps and reconfigurable structural colors. In this work, we describe a robust, water-based fabrication process for silk/inorganic hybrid one-dimensional (1D) photonic crystals that overcomes many of the conventional difficulties in ensuring reproducibility, uniformity, and reliability at the nanoscale.
View Article and Find Full Text PDFJ Inorg Biochem
September 2025
Department of Chemistry & Biochemistry, University of Montana, Missoula, MT 59812, United States; Center for Biomolecular Structure & Dynamics, University of Montana, Missoula, MT 59812, United States. Electronic address:
Omega loop C (residues 40-57) of cytochrome c (Cytc) is a common location for naturally-occurring variants of human Cytc that cause thrombocytopenia 4 (THC4). These variants are characterized by significant increases in the intrinsic peroxidase activity of Cytc, which appears to be linked to increased dynamics in Ω-loop D (residues 71-85). The mutations in Ω-loop C enhance the dynamics of Ω-loop D by decreasing the acid dissociation constant of the trigger group (pK) of the alkaline conformational transition.
View Article and Find Full Text PDF