Showing papers by "Kaixian Chen published in 2003"

Virtual Screening on Natural Products for Discovering Active Compounds and Target Information

Abstract: Natural products, containing inherently large-scale structural diversity than synthetic compounds, have been the major resources of bioactive agents and will continually play as protagonists for discovering new drugs. However, how to access this diverse chemical space efficiently and effectively is an exciting challenge for medicinal chemists and pharmacologists. While virtual screening, which has shown a great promise in drug discovery, will play an important role in digging out lead (active) compounds from natural products. This review focuses on the strategy of virtual screening based on molecular docking and, with successful examples from our laboratory, illustrates the efficiency of virtual screening in discovering active compounds from natural products. On the other hand, the sequencing of the human genome and numerous pathogen genomes has resulted in an unprecedented opportunity for discovering potential new drug targets. Chemogenomics has appeared as a new technology to initiate target discovery by using active compounds as probes to characterize proteome functions. Natural products are the ideal probes for such research. Binding affinity fingerprint is a powerful chemogenomic descriptor to characterize both small molecules and pharmacologically relevant proteins. Therefore, this review also discusses binding affinity fingerprint strategy for identifying target information from the genomic data by using natural products as the probes.

Differentiation of Cation-π Bonding from Cation-π Intermolecular Interactions: A Quantum Chemistry Study Using Density-Functional Theory and Morokuma Decomposition Methods

Abstract: A strong interaction called cation−π bonding, which we named because it occurs between aromatics and divalent metal cations, has been successfully differentiated from the normal cation−π intermolecular interactions. Our findings were based on the B3LYP/6-311++G(d,p) calculations and Morokuma decomposition analyses on the complexes formed by substituted benzenes with alkaline metal and alkaline earth metal ions. In comparison with the common cation−π intermolecular interaction, the cation−π bond in the complexes of either Be2+ or Mg2+ with the aromatics has its own characteristics: (a) short bond lengths, (b) very strong binding strength, (c) significant nonelectrostatic interaction that constitutes more than 50% of the total binding strength, (d) obvious cation−π orbital interaction, and (e) special orbital interaction pattern that only the π orbitals of the aromatics interact with the s, px, and py atomic orbitals of metal cations for forming bonding MOs. While the electrostatic interaction is significa...

Small envelope protein e of sars: cloning, expression, purification, cd determination, and bioinformatics analysis

Abstract: AIM: To obtain the pure sample of SARS small envelope E protein (SARS E protein), study its properties and analyze its possible functions. METHODS: The plasmid of SARS E protein was constructed by the polymerase chain reaction (PCR), and the protein was expressed in the E coli strain. The secondary structure feature of the protein was determined by circular dichroism (CD) technique. The possible functions of this protein were annotated by bioinformatics methods, and its possible three-dimensional model was constructed by molecular modeling. RESULTS: The pure sample of SARS E protein was obtained. The secondary structure feature derived from CD determination is similar to that from the secondary structure prediction. Bioinformatics analysis indicated that the key residues of SARS E protein were much conserved compared to the E proteins of other coronaviruses. In particular, the primary amino acid sequence of SARS E protein is much more similar to that of murine hepatitis virus (MHV) and other mammal coronaviruses. The transmembrane (TM) segment of the SARS E protein is relatively more conserved in the whole protein than other regions. CONCLUSION: The success of expressing the SARS E protein is a good starting point for investigating the structure and functions of this protein and SARS coronavirus itself as well. The SARS E protein may fold in water solution in a similar way as it in membrane-water mixed environment. It is possible that beta-sheet I of the SARS E protein interacts with the membrane surface via hydrogen bonding, this beta-sheet may uncoil to a random structure in water solution.

Putative hAPN receptor binding sites in SARS_CoV spike protein.

Abstract: AIM: To obtain the information of ligand-receptor binding between the S protein of SARS-CoV and CD13, identify the possible interacting domains or motifs related to binding sites, and provide clues for studying the functions of SARS proteins and designing anti-SARS drugs and vaccines. METHODS: On the basis of comparative genomics, the homology search, phylogenetic analyses, and multi-sequence alignment were used to predict CD13 related interacting domains and binding sites in the S protein of SARS-CoV. Molecular modeling and docking simulation methods were employed to address the interaction feature between CD13 and S protein of SARS-CoV in validating the bioinformatics predictions. RESULTS: Possible binding sites in the SARS-CoV S protein to CD13 have been mapped out by using bioinformatics analysis tools. The binding for one protein-protein interaction pair (D757-R761 motif of the SARS-CoV S protein to P585-A653 domain of CD13) has been simulated by molecular modeling and docking simulation methods. CONCLUSION: CD13 may be a possible receptor of the SARS-CoV S protein, which may be associated with the SARS infection. This study also provides a possible strategy for mapping the possible binding receptors of the proteins in a genome.

N-methylformamide-benzene complex as a prototypical peptide N-H…π hydrogen-bonded system: Density functional theory and MP2 studies

Abstract: Although the existence of peptide N−H···π hydrogen bonds recently has been reported in protein structures, little is known about their strength and binding nature and, therefore, the relative importance of the interaction. To shed light on this binding, the N-methylformamide−benzene complex, as a model of the peptide N−H···π hydrogen bonding, was studied by using density functional theory and Moller−Plesset second-order perturbation (MP2) methods. The geometry of the complex was fully optimized at the B3LYP/6-31G(d,p) and MP2/6-31G(d,p) levels. The optimized interaction distances are about 3.6 and 3.2 A, respectively, at the two levels. The binding energy corrected by basis set superposition error with the MP2/cc-pVTZ method based on the MP2/6-31G** geometry is −4.37 kcal/mol, which is as strong as the conventional hydrogen bonding. The calculated results suggest that the peptide N−H···π hydrogen bonding is of sufficient strength to play an important role in the stabilization of protein structures. These ...

Identification of probable genomic packaging signal sequence from SARS-CoV genome by bioinformatics analysis.

Abstract: AIM: To predict the probable genomic packaging signal of SARS-CoV by bioinformatics analysis. The derived packaging signal may be used to design antisense RNA and RNA interfere (RNAi) drugs treating SARS. METHODS: Based on the studies about the genomic packaging signals of MHV and BCoV, especially the information about primary and secondary structures, the putative genomic packaging signal of SARS-CoV were analyzed by using bioinformatic tools. Multi-alignment for the genomic sequences was performed among SARS-CoV, MHV, BCoV, PEDV and HCoV 229E. Secondary structures of RNA sequences were also predicted for the identification of the possible genomic packaging signals. Meanwhile, the N and M proteins of all five viruses were analyzed to study the evolutionary relationship with genomic packaging signals. RESULTS: The putative genomic packaging signal of SARS-CoV locates at the 3' end of ORF1b near that of MHV and BCoV, where is the most variable region of this gene. The RNA secondary structure of SARS-CoV genomic packaging signal is very similar to that of MHV and BCoV. The same result was also obtained in studying the genomic packaging signals of PEDV and HCoV 229E. Further more, the genomic sequence multi-alignment indicated that the locations of packaging signals of SARS-CoV, PEDV, and HCoV overlaped each other. It seems that the mutation rate of packaging signal sequences is much higher than the N protein, while only subtle variations for the M protein. CONCLUSIONS: The probable genomic packaging signal of SARS-CoV is analogous to that of MHV and BCoV, with the corresponding secondary RNA structure locating at the similar region of ORF1b. The positions where genomic packaging signals exist have suffered rounds of mutations, which may influence the primary structures of the N and M proteins consequently.

Benzopyran compounds, process for preparing the same and their use

Abstract: The invention relates to the benzopyran compounds of formula (I), or the salts thereof, in which, the bond between 3 and 4 positions is a single or double bond; R 1 represents a hydrogen atom or a C 1-6 alkyl that can be substituted; R 2 represents a hydrogen atom, a C 1-6 alkyl that can be substituted or an aromatic carbocyclic or aromatic heterocyclic group that can be substituted The invention also relates to a process for preparing such compounds or their salts as well as the use of such compounds or their salts in the preparation of the medicine against type II diabetes mellitus