Faculty of Chemistry, University of Gdańsk, Fahrenheit Union of Universities in Gdańsk, Gdańsk, Poland.
Centre of Informatics Tri-city Academic Supercomputer and Network (CI TASK), Gdańsk University of Technology, Fahrenheit Union of Universities in Gdańsk, Gdańsk, Poland.
Methods Mol Biol. 2025;2870:267-288. doi: 10.1007/978-1-0716-4213-9_14.
Coarse graining is usually considered as a tool to extend the time and size scale of simulations. However, leaving out the atomistic details to keep their fingerprints in a coarse-grained model also enables us to understand better structure formation and dynamics. In this chapter, by using our scale-consistent theory of coarse graining, we demonstrate that the coarse-grained terms corresponding to the coupling between local conformational states of amino-acid residues explain secondary-structure propagation along polypeptide backbone to stabilize -helices and -strands in proteins and direct the loops preceding and following such segments of protein structure. These and related correlations are probably the still missing terms in both physics- and knowledge-based approaches to protein-structure modeling, including AlphaFold. We also show that the chirality of coarse-grained torsional potentials and, thereby, that of polypeptide backbone emerge from putting together achiral site-based torsional potentials given the phase shift due to residue chirality, and that the improper-torsional potentials that correspond to the coupling between local conformational states of the sites adjacent to a given -carbon atom enable us to model amino-acid-residue enantiomerization.
粗粒化通常被认为是一种扩展模拟时间和空间尺度的工具。然而，通过忽略原子细节，在粗粒化模型中保留它们的特征，我们也能够更好地理解结构形成和动力学。在本章中，我们通过使用我们的粗粒化尺度一致性理论，证明了对应于氨基酸残基局部构象状态之间耦合的粗粒化项，可以解释二级结构沿着多肽主链的传播，从而稳定蛋白质中的α-螺旋和β-折叠，并指导位于这些蛋白质结构片段之前和之后的环。这些和相关的相关性可能是蛋白质结构建模的物理和基于知识的方法中仍然缺失的项，包括 AlphaFold。我们还表明，粗粒化扭转势的手性，以及由此产生的多肽主链的手性，是从给定残基手性引起的位相移，将基于位的非手性扭转势组合在一起而产生的，而对应于相邻给定碳原子的局部构象状态之间耦合的非规范扭转势使我们能够对氨基酸残基对映异构体化进行建模。
