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1.  Contact-based ligand-clustering approach for the identification of active compounds in virtual screening 
Evaluation of docking results is one of the most important problems for virtual screening and in silico drug design. Modern approaches for the identification of active compounds in a large data set of docked molecules use energy scoring functions. One of the general and most significant limitations of these methods relates to inaccurate binding energy estimation, which results in false scoring of docked compounds. Automatic analysis of poses using self-organizing maps (AuPosSOM) represents an alternative approach for the evaluation of docking results based on the clustering of compounds by the similarity of their contacts with the receptor. A scoring function was developed for the identification of the active compounds in the AuPosSOM clustered dataset. In addition, the AuPosSOM efficiency for the clustering of compounds and the identification of key contacts considered as important for its activity, were also improved. Benchmark tests for several targets revealed that together with the developed scoring function, AuPosSOM represents a good alternative to the energy-based scoring functions for the evaluation of docking results.
doi:10.2147/AABC.S30881
PMCID: PMC3459543  PMID: 23055752
scoring; docking; virtual screening; CAR; AuPosSOM
2.  NMR solution structure and function of the C-terminal domain of eukaryotic class 1 polypeptide chain release factor 
The Febs Journal  2010;277(12):2611-2627.
Termination of translation in eukaryotes is triggered by two polypeptide chain release factors, eukaryotic class 1 polypeptide chain release factor (eRF1) and eukaryotic class 2 polypeptide chain release factor 3. eRF1 is a three-domain protein that interacts with eukaryotic class 2 polypeptide chain release factor 3 via its C-terminal domain (C-domain). The high-resolution NMR structure of the human C-domain (residues 277–437) has been determined in solution. The overall fold and the structure of the β-strand core of the protein in solution are similar to those found in the crystal structure. The structure of the minidomain (residues 329–372), which was ill-defined in the crystal structure, has been determined in solution. The protein backbone dynamics, studied using 15N-relaxation experiments, showed that the C-terminal tail 414–437 and the minidomain are the most flexible parts of the human C-domain. The minidomain exists in solution in two conformational states, slowly interconverting on the NMR timescale. Superposition of this NMR solution structure of the human C-domain onto the available crystal structure of full-length human eRF1 shows that the minidomain is close to the stop codon-recognizing N-terminal domain. Mutations in the tip of the minidomain were found to affect the stop codon specificity of the factor. The results provide new insights into the possible role of the C-domain in the process of translation termination.
doi:10.1111/j.1742-464X.2010.07672.x
PMCID: PMC2909394
human eukaryotic class 1 polypeptide chain release factor (eRF1); NMR structure and dynamics; stop codon recognition specificity; termination of protein synthesis
3.  NMR solution structure and function of the C-terminal domain of eukaryotic class 1 polypeptide chain release factor 
The Febs Journal  2010;277(12):2611-2627.
Termination of translation in eukaryotes is triggered by two polypeptide chain release factors, eukaryotic class 1 polypeptide chain release factor (eRF1) and eukaryotic class 2 polypeptide chain release factor 3. eRF1 is a three-domain protein that interacts with eukaryotic class 2 polypeptide chain release factor 3 via its C-terminal domain (C-domain). The high-resolution NMR structure of the human C-domain (residues 277–437) has been determined in solution. The overall fold and the structure of the β-strand core of the protein in solution are similar to those found in the crystal structure. The structure of the minidomain (residues 329–372), which was ill-defined in the crystal structure, has been determined in solution. The protein backbone dynamics, studied using 15N-relaxation experiments, showed that the C-terminal tail 414–437 and the minidomain are the most flexible parts of the human C-domain. The minidomain exists in solution in two conformational states, slowly interconverting on the NMR timescale. Superposition of this NMR solution structure of the human C-domain onto the available crystal structure of full-length human eRF1 shows that the minidomain is close to the stop codon-recognizing N-terminal domain. Mutations in the tip of the minidomain were found to affect the stop codon specificity of the factor. The results provide new insights into the possible role of the C-domain in the process of translation termination.
doi:10.1111/j.1742-4658.2010.07672.x
PMCID: PMC2984548  PMID: 20553496
human eukaryotic class 1 polypeptide chain release factor (eRF1); NMR structure and dynamics; stop codon recognition specificity; termination of protein synthesis

Results 1-3 (3)