A comprehensive conformational analysis of tryptophan,its ionic and dimeric forms

Tryptophan is an essential amino acid, and understanding the conformational preferences of monomer and dimer is a subject of outstanding relevance in biological systems. An exhaustive first principles investigation of tryptophan ( W ) and its ionized counterparts cations (WC) , anions (WA) , and zwitterions (WZ) has been carried out. A comprehensive and systematic study of tryptophan dimer (WD) conformations resulted in about 62 distinct minima on the potential energy surface. The hydrogen bonds and a variety of noncovalent interactions such as OH‐π, NH‐π, CH‐π, CH‐O, and π‐π interactions stabilized different forms of tryptophan and its dimers. Over all in monomeric conformers which have NH‐O, hydrogen bonds showed higher stability than other conformers. A cursory analysis reveal that the most stable dimers stabilized by hydrogen bonding interactions while the less stable dimers showed aromatic side chain interactions. Protein Data Bank analysis of tryptophan dimers reveals that at a larger distance greater than 5 Å, T‐shaped orientations (CH‐π interactions) are more prevalent, while stacked orientations (π‐π interactions) are predominant at a smaller distance. © 2013 Wiley Periodicals, Inc.     

生物催化在绿色化学和新药开发中的应用

近年来生物技术领域有了突破性进展,如: 公共基因数据库(GenBank)和蛋白质数据库(PDB)中序列的指数增长,高效基因克隆和表达平台的建立,可有效改进生物催化剂专一性、选择性和稳定性的酶定向进化技术的应用。这些进展使生物催化在化学合成中日趋重要[1]。本文综述了生物催化在如下领域的成功应用：在药物生产中用于开发经济的化学酶法合成工艺,在绿色化学领域中最大程度的减少废物的产生和危险试剂的应用,在天然化学领域中对天然产物进行修饰以发现具有更好生物活性的新药物。     

Is the rigid-body assumption reasonable?: Insights into the effects of dynamics on the electrostatic analysis of barnase-barstar

Electrostatically-driven association of proteins is important to many biological functions, and understanding which amino acid residues contribute to these interactions is crucial to protein design. Theoretical calculations that are used to elucidate the role of electrostatics in association are typically based on a single experimentally determined protein structure, while an underlying rigid-body assumption is adopted. The goal of this study was to investigate the role of conformational fluctuations on electrostatic interaction energies, as applied to the electrostatic analysis of barnase-barstar. For our calculations, we apply theoretical alanine-scan mutagenesis to introduce charge perturbations by replacing every ionizable residue with alanine, one at a time. Electrostatic clustering and free energy calculations based on the Poisson-Boltzmann method are used to evaluate the effects of each perturbation. Molecular dynamics simulations are performed for the barnase-barstar parent complex and seven experimental alanine mutations from the literature, in order to introduce relaxation before and after mutation. We discuss the effects of dynamics, in the form of pre- and post-mutation relaxation, on electrostatic clustering and free energies of association in light of experimental data. We also examine the utility of nine electrostatic similarity methods for clustering of barnase alanine-scan mutants. Our calculations suggest that the rigid-body assumption is reasonable for electrostatic calculations of barnase-barstar.     

π-Hole Interactions Involving Nitro Aromatic Ligands in Protein Structures

Studying noncanonical intermolecular interactions between a ligand and a protein constitutes an emerging research field. Identifying synthetically accessible molecular fragments that can engage in intermolecular interactions is a key objective in this area. Here, it is shown that so-called “π-hole interactions” are present between the nitro moiety in nitro aromatic ligands and lone pairs within protein structures (water and protein carbonyls and sulfurs). Ample structural evidence was found in a PDB analysis and computations reveal interaction energies of about −5 kcal mol⁻¹ for ligand–protein π-hole interactions. Several examples are highlighted for which a π-hole interaction is implicated in the superior binding affinity or inhibition of a nitro aromatic ligand versus a similar non-nitro analogue. The discovery that π-hole interactions with nitro aromatics are significant within protein structures parallels the finding that halogen bonds are biologically relevant. This has implications for the interpretation of ligand–protein complexation phenomena, for example, involving the more than 50 approved drugs that contain a nitro aromatic moiety.     

ProSeg: a database of local structures of protein segments

Integration of knowledge on the sequence-structure correlation of proteins provides a basis for the structural design of artificial novel proteins. As one of strategies, it is effective to consider a short segment, whose size is in between an amino acid and a domain, as a correlation unit for exploring the structure-to-sequence relationship. Here we report the development of a database called ProSeg, which consists of two sub-databases, Segment DB and Cluster DB. Segment DB contains tens of thousands of segments that were prepared by dividing the primary sequences of 370 proteins using a sliding L-residue window (L = 5, 9, 11, 15). These segments were classified into several thousands of clusters according to their three-dimensional structural resemblance. Cluster DB contains much cluster-related information, which includes image, rank, frequency, secondary structure assignment, sequence profile, etc. Users can search for a suitable cluster by inputting an appropriate parameter (i.e., PDB ID, dihedral angles, or DSSP symbols), which identifies the backbone structure of a query segment. Analogous to a language, ProSeg could be regarded as a ‘structure-sequence dictionary’ that contains over 10,000 ‘protein words’. ProSeg is freely accessible through the Internet ().     

一种蛋白质三维结构中残基重心的计算方法

基于蛋白质三维结构数据PDB,给出一种蛋白质残基重心的计算方法,同时阐述该方法的python语言的实现过程.该方法不需要知道残基侧链原子的坐标,只需知道主链上原子的坐标即可计算蛋白质残基间的距离.     

AutoCAD环境下对话框的设计开发

本文在花园路径地砖铺设参数化设计中，以参数输入对话框开发为例，说明在ＡｕｔｏＣＡＤＲ１３境下开发实现一个对话框的方法，该方法也适用于以ＡｕｔｏＣＡＤＲ１２以上版本为支撑环的参数化设计应用软件界面设计。     

Protein Data Bank中抗体的自动识别

我们发展了一种名为KIAb（Keyword-based Identification of Antibodies）的方法用于自动识别Protein Data Bank（PDB）中的抗体结构。该方法通过读取PDB格式的文件，查找与抗体相关的特定关键词并做出判断。我们使用该方法从PDB中识别出780个结构文件，经人工检查其中767个为抗体，成功率高达98.3%。结果基本包括了抗体结构数据库Summary of Antibody Crystal Structures（SACS）中收录的所有条目，而且还包括该数据库没有收录的34个抗体结构。因此该方法对PDB数据库中抗体的识别更为完备而且具有很低的假阳性率。     

Estimating structure quality trends in the Protein Data Bank by equivalent resolution

The quality of protein structures obtained by different experimental and ab-initio calculation methods varies considerably. The methods have been evolving over time by improving both experimental designs and computational techniques, and since the primary aim of these developments is the procurement of reliable and high-quality data, better techniques resulted on average in an evolution toward higher quality structures in the Protein Data Bank (PDB). Each method leaves a specific quantitative and qualitative “trace” in the PDB entry. Certain information relevant to one method (e.g. dynamics for NMR) may be lacking for another method. Furthermore, some standard measures of quality for one method cannot be calculated for other experimental methods, e.g. crystal resolution or NMR bundle RMSD. Consequently, structures are classified in the PDB by the method used. Here we introduce a method to estimate a measure of equivalent X-ray resolution (e-resolution), expressed in units of Å, to assess the quality of any type of monomeric, single-chain protein structure, irrespective of the experimental structure determination method. We showed and compared the trends in the quality of structures in the Protein Data Bank over the last two decades for five different experimental techniques, excluding theoretical structure predictions. We observed that as new methods are introduced, they undergo a rapid method development evolution: within several years the e-resolution score becomes similar for structures obtained from the five methods and they improve from initially poor performance to acceptable quality, comparable with previously established methods, the performance of which is essentially stable.     

IBM PC微机上的蛋白质数据库及其管理系统

在IBM PC微机上建立了一个蛋白质数据库及其管理分析系统。