Proteins are essential parts of living organisms and participate in virtually every process within cells. As the genomic sequences for increasing number of organisms are completed, research into how proteins can perform such a variety of functions has become much more intensive because the value of the genomic sequences relies on the accuracy of understanding the encoded gene products. Although the static three-dimensional structures of many proteins are known, the functions of proteins are ultimately governed by their dynamic characteristics, including the folding process, conformational fluctuations, molecular motions, and protein-ligand interactions. In this review, the physicochemical principles underlying these dynamic processes are discussed in depth based on the free energy landscape (FEL) theory. Questions of why and how proteins fold into their native conformational states, why proteins are inherently dynamic, and how their dynamic personalities govern protein functions are answered. This paper will contribute to the understanding of structure-function relationship of proteins in the post-genome era of life science research. free energy landscape, entropy-enthalpy non-complementarity, ruggedness, driving force, thermodynamics, kinetics Citation:Li HM, Xie YH, Liu CQ, Liu SQ. Physicochemical bases for protein folding, dynamics, and protein-ligand binding.
A new integrated sequence-structure database, called IADE (Integrated ASTRAL-DSSP-EMBL), incorporating matching mRNA sequence, amino acid sequence, and protein secondary structural data, is constructed. It includes 648 protein domains. Based on the IADE database, we studied the relation between RNA stem-loop frequencies and protein secondary structure. It was found that the alpha-helices and beta-strands on proteins tend to be preferably "coded" by mRNA stem region, while the coils on proteins tend to be preferably "coded" by mRNA loop region. These tendencies are more obvious if we observe the structural words (SWs). An SW is defined by a four-amino-acid-fragment that shows the pronounced secondary structural (alpha-helix or beta-strand) propensity. It is demonstrated that the deduced correlation between protein and mRNA structure can hardly be explained as the stochastic fluctuation effect.
CCR2b, a chemokine receptor for MCP-1, -2, -3, -4, plays an important role in a variety of diseases involving infection, inflammation, and/or injury, as well as being a coreceptor for HIV-1 infection. Two models of human CCR2b (hCCR2b) were generated by homology modeling and 1 ns restrained molecular dynamics (MD) simulation. In one only C113-C190 forms a disulfide bond (SS model); in another the potential C32-C277 disulfide bond was formed (2SS model). Analysis of the structures and averaged displacements of Calpha atoms of the N-terminal residues shows that the main differences between the SS and 2SS models lie in a region D25YDYGAPCHKFD36; in the extracellular part of the 2SS model the accessible surfaces of N12, F23, Y26, Y28 and F35 are obviously raised and a more stable H-bond net is formed. The potential energy of the 2SS-water assembly finally fluctuated around -43,020 kJ x mol(-1), which is about 302 kJ x mol(-1) lower than that of the SS-water assembly. All these results suggest that the 2SS model is more favorable. The CCR2b genes of 17 primates were sequenced and four CCR2b models for primates Ateles paniscus (A. pan), Hylobates leucogyneus(H. leu), Papio cynocephalus (P. cyn) and Trachypithecus francoist ( T. fra) were generated based on the 2SS model. A comparison of hCCR2b with primate CCR2b also supports the importance of the region D25YDYGAPCHKFD36. Electrostatic potential maps of human and primate CCR2b all display the dipolar characteristics of CCR2b with the negative pole located in the extracellular part and a strong positive pole in the cytoplasmic part. Based on the CCR2b model, we suggest that the main functional residues fall in the D25YDYGAPCHKFD36 region, and the negative electrostatic feature is a non-specific, but necessary, factor for ligands or gp120/CD4 binding.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.