Analytical molecular surface calculation

Connolly, Michael L.

doi:10.1107/s0021889883010985

Cited by 2,372 publications

(1,686 citation statements)

References 3 publications

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“…PatchDock is geometry-based molecular docking tool. In PatchDock the molecule's surface is divided into convex, concave and flat surfaces patches [11,12]. The surfaces of ligand and protein are distributed into patches of above surfaces and searched for their complementary patch.…”

Section: Receptor-ligand Interactionsmentioning

confidence: 99%

Potential entry inhibitors of the envelope protein (E2) of Chikungunya virus: in silico structural modeling, docking and molecular dynamic studies

et al. 2017

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Chikungunya fever is an arboviral infection caused by the Chikungunya virus (CHIKV) and is transmitted by Aedes mosquito. The envelope protein (E2) of Chikungunya virus is involved in attachment of virion with the host cell. The present study was conceptualized to determine the structure of E2 protein of CHIKV and to identify the potential viral entry inhibitors. The secondary and tertiary structure of E2 protein was determined using bioinformatics tools. The mutational analysis of the E2 protein suggested that mutations may stabilize or de-stabilize the structure which may affect the structure-function relationship. In silico screening of various compounds from different databases identified two lead molecules i.e. phenothiazine and bafilomycin. Molecular docking and MD simulation studies of the E2 protein and compound complexes was carried out. This analysis revealed that bafilomycin has high docking score and thus high binding affinity with E2 protein suggesting stable protein-ligand interaction. Further, MD simulations suggested that both the compounds were stabilizing E2 protein. Thus, bafilomycin and phenothiazine may be considered as the lead compounds in terms of potential entry inhibitor for CHIKV. Further, these results should be confirmed by comprehensive cell culture, cytotoxic assays and animal experiments. Certain derivatives of phenothiazines can also be explored in future studies for entry inhibitors against CHIKV. The present investigation thus provides insight into protein structural dynamics of the envelope protein of CHIKV. In addition the study also provides information on the dynamics of interaction of E2 protein with entry inhibitors that will contribute towards structure based drug design.

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Section: Receptor-ligand Interactionsmentioning

confidence: 99%

Potential entry inhibitors of the envelope protein (E2) of Chikungunya virus: in silico structural modeling, docking and molecular dynamic studies

et al. 2017

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“…The changes in the molecular surface and the solvent-accessible surface (Richards, 1977) were calculated using simple analytic expressions for the dimerization reactions (see below) and using the MSCON (Connolly, 1983) and NACCESS (Hubbard & Thornton, 1993) programs for the multibody reactions. For comparison to the PMF calculations, surface area changes were converted to free energy changes using scale factors of 0.025 kcal/A2 and 0.1 10 kcal/A2 for the solvent-accessible surface and the molecular surface, respectively (Jackson & Sternberg, 1994).…”

Section: Sudace Area Calculationsmentioning

confidence: 99%

A desolvation barrier to hydrophobic cluster formation may contribute to the rate‐limiting step in protein folding

1997

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To gain insight into the free energy changes accompanying protein hydrophobic core formation, we have used computer simulations to study the formation of small clusters of nonpolar solutes in water. A barrier to association is observed at the largest solute separation that does not allow substantial solvent penetration. The barrier reflects an effective increase in the size of the cavity occupied by the expanded but water-excluding cluster relative to both the close-packed cluster and the fully solvated separated solutes; a similar effect may contribute to the barrier to protein foldinghnfolding. Importantly for the simulation of protein folding without explicit solvent, we find that the interactions between nonpolar solutes of varying size and number can be approximated by a linear function of the molecular surface, but not the solvent-accessible surface of the solutes. Comparison of the free energy of cluster formation to that of dimer formation suggests that the assumption of pair additivity implicit in current protein database derived potentials may be in error. Keywords: hydrophobic interaction; potential of mean force; protein foldingThe hydrophobic interaction is extremely important in the folding and stabilization of proteins (Kauzmann, 1959;Dill, 1990), but is relatively poorly understood. In spite of this poor understanding, computer modeling of protein folding has developed substantially over the past IO years. One approach is to simulate protein folding in the presence of explicitly modeled water molecules, which, depending upon the accuracy of the water model, should at least in part reproduce the hydrophobic interaction. Molecular dynamics simulations with an explicit solvent model have provided valuable insights into possible foldinghnfolding trajectories (Daggett & Levitt, 1994;Karplus & Sali, 1995). However, because of the complexity of the processes being simulated and the absence of an obvious reaction coordinate, most studies have focused on qualitative features of the trajectories and not sought to calculate free energy changes (the study of Brooks and Boczko [I9951 is an exception). A second approach avoids the complexity and high computational demands of simulations with hundreds of explicit water molecules by deriving effective potentials from the distribution of amino acid residues in known protein structures (reviewed in Jones & Thornton, 1996). Although not modeled explicitly, the hydrophobic interaction dominates such "knowledge-based' potentials. These relationships are not true interaction potentials in a rigorous sense, but they have been extremely useful in a wide variety of applications, including protein fold recognition (Jones &

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“…3). The accessible surface area calculations are performed on the proteins using the Connolly molecular surface program (Connolly, 1983a(Connolly, , 1983b) with a 1.4-A-radius probe. Surface residues are defined as those with areas greater than or equal to 10.0 A'.…”

Section: Calculation Of Buried Surfacesmentioning

confidence: 99%

A role for surface hydrophobicity in protein‐protein recognition

1994

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The role of hydrophobicity as a determinant of protein-protein interactions is examined. Surfaces of apo-protein targets comprising 9 classes of enzymes, 7 antibody fragments, hirudin, growth hormone, and retinol-binding protein, and their associated ligands with available X-ray structures for their complexed forms, are scanned to determine clusters of surface-accessible amino acids. Clusters of surface residues are ranked on the basis of the hydrophobicity of their constituent amino acids. The results indicate that the location of the co-crystallized ligand is commonly found to correspond with one of the strongest hydrophobic clusters on the surface of the target molecule. In 25 of 38 cases, the correspondence is exact, with the position of the most hydrophobic cluster coinciding with more than one-third of the surface buried by the bound ligand. The remaining 13 cases demonstrate this correspondence within the top 6 hydrophobic clusters. These results suggest that surface hydrophobicity can be used to identify regions of a protein's surface most likely to interact with a binding ligand. This fast and simple procedure may be useful for identifying small sets of well-defined loci for possible ligand attachment.

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Analytical molecular surface calculation

Cited by 2,372 publications

References 3 publications

Potential entry inhibitors of the envelope protein (E2) of Chikungunya virus: in silico structural modeling, docking and molecular dynamic studies

Potential entry inhibitors of the envelope protein (E2) of Chikungunya virus: in silico structural modeling, docking and molecular dynamic studies

A desolvation barrier to hydrophobic cluster formation may contribute to the rate‐limiting step in protein folding

A role for surface hydrophobicity in protein‐protein recognition

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