The folding dynamics and structural characteristics of peptides RTKAWNRQLYPEW （P1） and RTKQLYPEW （P2） are investigated by using all-atomic simulation procedure CHARMM in this work. The results show that P1, a segment of an antigen, has a folding motif of α-helix, whereas P2, which is derived by deleting four residues AWNR from peptide P1, prevents the formation of helix and presents a β-strand. And peptlde P1 experiences a more rugged energy landscape than peptide P2. From our results, it is inferred that the antibody CD8 cytolytic T lymphocyte prefers an antigen with a β-folding structure to that with an α-helical one.
在原子水平上发展了一种距离相关的用于研究蛋白质-蛋白质相互作用的平均势(potential of mean force,简称PMF)方法.与传统理论模型相比,我们的模型考虑了蛋白质系统的复杂环境因素.这种改进使得该模型能够给出物理上更合理和准确的势函数形式.得到这样的势函数是正确描述蛋白质结构及相互作用的前提条件.而且借助于改进后的方法,还可以对蛋白质中残基相互作用的空间拓扑规律进行研究.期望这种改进将促进平均势方法在蛋白质科学其他领域,如蛋白质折叠识别,结构预测及热稳定性预测中的应用和发展.
In this work, we make an investigation on the preferences of orientations between amino acids using the orientation defined based on the local geometry of the amino acids concerned. It is found that there are common preferences of orientations （70°, 30°, 140°） and （110°, 340°, 100°） for various pairs of amino acids. Different side chains may strengthen or weaken the common preferences, which is related to the effect of packing. Some amino acids having specific local flexibility may possess some preferences of orientations besides the common ones, such as （10°, 280°, 210°）. Another analysis on the pairs of the amino acids with different secondary-structure preferences shows that the directional interaction may affect the distribution of orientation more effectively than the packing or local flexibility. All these results provide us some insight of the organization of amino acids in protein, and their relation with some related interactions.
Sequence alignment is a common method for finding protein structurally conserved/similar regions. However, sequence alignment is often not accurate if sequence identities between to-be-aligned se- quences are less than 30%. This is because that for these sequences, different residues may play similar structural roles and they are incorrectly aligned during the sequence alignment using substitu- tion matrix consisting of 20 types of residues. Based on the similarity of physicochemical features, residues can be clustered into a few groups. Using such simplified alphabets, the complexity of protein sequences is reduced and at the same time the key information encoded in the sequences remains. As a result, the accuracy of sequence alignment might be improved if the residues are properly clustered. Here, by using a database of aligned protein structures (DAPS), a new clustering method based on the substitution scores is proposed for the grouping of residues, and substitution matrices of residues at different levels of simplification are constructed. The validity of the reduced alphabets is confirmed by relative entropy analysis. The reduced alphabets are applied to recognition of protein structurally conserved/similar regions by sequence alignment. The results indicate that the accuracy or efficiency of sequence alignment can be improved with the optimal reduced alphabet with N around 9.
LI Jing1 & WANG Wei1,2 1 National Laboratory of Solid State Microstructure and Department of Physics, Nanjing University, Nanjing 210093, China
