Molecular docking programs play a crucial role in drug design and development. In recent years, much attention has been devoted to the protein-peptide docking problem in which docking of a flexible peptide with a know...Molecular docking programs play a crucial role in drug design and development. In recent years, much attention has been devoted to the protein-peptide docking problem in which docking of a flexible peptide with a known protein is sought. In this work we present a new docking algorithm which is based on the use of a filling function method for continuos constrained global optimization. Indeed, the protein-peptide docking position is sought by minimizing the conformational potential energy subject to constraints necessary to maintain the primary sequence of the given peptide. The resulting global optimization problem is difficult mainly for two reasons. First, the problem is large scale in constrained global optimization;second, the energy function is multivariate non-convex so that it has many local minima. The method is based on the device of modifying the original objective function once a local minimum has been attained by adding to it a filling term. This allows the overall algorithm to escape from local minima thus, ultimately, giving the algorithm ability to explore large regions in the peptide conformational space. We present numerical results on a set of benchmark docking pairs and comparison with the well-known software package for molecular docking PacthDock.展开更多
Protein-peptide interactions, where one partner is a globular protein （domain） and the other is a flexible linear peptide, are key components of cellular processes predominantly in signal- ing and regulatory network...Protein-peptide interactions, where one partner is a globular protein （domain） and the other is a flexible linear peptide, are key components of cellular processes predominantly in signal- ing and regulatory networks, hence are prime targets for drug design. To derive the details of the protein-peptide interaction mechanism is often a cumbersome task, though it can be made easier with the availability of specific databases and tools. The Peptide Binding Protein Database （Pep- Bind） is a curated and searchable repository of the structures, sequences and experimental observa- tions of 3100 protein^eptide complexes. The web interface contains a computational tool, protein inter-chain interaction （PICI）, for computing several types of weak or strong interactions at the pro- tein peptide interaction interface and visualizing the identified interactions between residues in Jmol viewer. This initial database release focuses on providing protein-peptide interface informa- tion along with structure and sequence information for protein-peptide complexes deposited in the Protein Data Bank （PDB）. Structures in PepBind are classified based on their cellular activity. More than 40% of the structures in the database are found to be involved in different regulatory pathways and nearly 20% in the immune system. These data indicate the importance of protein- peptide complexes in the regulation of cellular processes. PepBind is freely accessible at http：// pepbind.bicpu.edu.in/.展开更多
Human UBC9 is a member of the E2 family of proteins. However, instead of conjugating to ubiquitin, it conjugates to a ubiquitin homologue SUMO-1 (also known as UBL1, GMP1, SMTP3, PICT-1 and sentrin). The SUMO-1 conjug...Human UBC9 is a member of the E2 family of proteins. However, instead of conjugating to ubiquitin, it conjugates to a ubiquitin homologue SUMO-1 (also known as UBL1, GMP1, SMTP3, PICT-1 and sentrin). The SUMO-1 conjugation pathway is very similar to that of ubiquitin with regard to the primary sequences of the ubiquitin activating enzymes (E1), the three-dimensional structures of the ubiquitin conjugating enzymes (E2), and the chemistry of the overall conjugation pathway. The interaction of p53 and UBC9, the E2 of the SUMO-1 pathway, has been studied by nuclear magnetic resonance spectroscopy. A peptide corresponding to the nuclear localization domain of p53 specifically interacts with UBC9 and this interaction is likely to be important for conjugation of p53 with SUMO-1. The largest chemical shift changes on UBC9 occur at residues 94 and 129-135. This region is adjacent to the active site and has significant dynamic behavior on the μs-ms and ps-ns timescales. Correlation of chemical shift changes and mobility of these residues further suggest the importance of these residues in substrate recognition.展开更多
文摘Molecular docking programs play a crucial role in drug design and development. In recent years, much attention has been devoted to the protein-peptide docking problem in which docking of a flexible peptide with a known protein is sought. In this work we present a new docking algorithm which is based on the use of a filling function method for continuos constrained global optimization. Indeed, the protein-peptide docking position is sought by minimizing the conformational potential energy subject to constraints necessary to maintain the primary sequence of the given peptide. The resulting global optimization problem is difficult mainly for two reasons. First, the problem is large scale in constrained global optimization;second, the energy function is multivariate non-convex so that it has many local minima. The method is based on the device of modifying the original objective function once a local minimum has been attained by adding to it a filling term. This allows the overall algorithm to escape from local minima thus, ultimately, giving the algorithm ability to explore large regions in the peptide conformational space. We present numerical results on a set of benchmark docking pairs and comparison with the well-known software package for molecular docking PacthDock.
基金the Department of Biotechnology (Grant No. BT/BI/03/015/2002)Department of Information Technology (Grant No. DIT/R&D/15 (9)2007), Government of India
文摘Protein-peptide interactions, where one partner is a globular protein （domain） and the other is a flexible linear peptide, are key components of cellular processes predominantly in signal- ing and regulatory networks, hence are prime targets for drug design. To derive the details of the protein-peptide interaction mechanism is often a cumbersome task, though it can be made easier with the availability of specific databases and tools. The Peptide Binding Protein Database （Pep- Bind） is a curated and searchable repository of the structures, sequences and experimental observa- tions of 3100 protein^eptide complexes. The web interface contains a computational tool, protein inter-chain interaction （PICI）, for computing several types of weak or strong interactions at the pro- tein peptide interaction interface and visualizing the identified interactions between residues in Jmol viewer. This initial database release focuses on providing protein-peptide interface informa- tion along with structure and sequence information for protein-peptide complexes deposited in the Protein Data Bank （PDB）. Structures in PepBind are classified based on their cellular activity. More than 40% of the structures in the database are found to be involved in different regulatory pathways and nearly 20% in the immune system. These data indicate the importance of protein- peptide complexes in the regulation of cellular processes. PepBind is freely accessible at http：// pepbind.bicpu.edu.in/.
文摘Human UBC9 is a member of the E2 family of proteins. However, instead of conjugating to ubiquitin, it conjugates to a ubiquitin homologue SUMO-1 (also known as UBL1, GMP1, SMTP3, PICT-1 and sentrin). The SUMO-1 conjugation pathway is very similar to that of ubiquitin with regard to the primary sequences of the ubiquitin activating enzymes (E1), the three-dimensional structures of the ubiquitin conjugating enzymes (E2), and the chemistry of the overall conjugation pathway. The interaction of p53 and UBC9, the E2 of the SUMO-1 pathway, has been studied by nuclear magnetic resonance spectroscopy. A peptide corresponding to the nuclear localization domain of p53 specifically interacts with UBC9 and this interaction is likely to be important for conjugation of p53 with SUMO-1. The largest chemical shift changes on UBC9 occur at residues 94 and 129-135. This region is adjacent to the active site and has significant dynamic behavior on the μs-ms and ps-ns timescales. Correlation of chemical shift changes and mobility of these residues further suggest the importance of these residues in substrate recognition.
