A simple statistical method for discriminating outer membrane proteins with better accuracy.

Motivation: Discriminating outer membrane proteins from other folding types of globular and membrane proteins is an important task both for identifying outer membrane proteins from genomic sequences and for the successful prediction of their secondary and tertiary structures.

Results: We have systematically analyzed the amino acid composition of globular proteins from different structural classes and outer membrane proteins. We found that the residues, Glu, His, Ile, Cys, Gln, Asn and Ser, show a significant difference between globular and outer membrane proteins.

Characteristic features of amino acid residues in coiled-coil protein structures.

Detailed analyses of protein structures provide an opportunity to understand conformation and function in terms of amino acid sequence and composition. In this work, we have systematically analyzed the characteristic features of the amino acid residues found in alpha-helical coiled-coils and, in so doing, have developed indices for their properties, conformational parameters, surrounding hydrophobicity and flexibility. As expected, there is preference for hydrophobic (Ala, Leu), positive (Lys, Arg) and negatively (Glu) charged residues in coiled-coil domains.

Look-up tables for protein solvent accessibility prediction and nearest neighbor effect analysis.

We developed dictionaries of two-, three-, and five-residue patterns in proteins and computed the average solvent accessibility of the central residues in their native proteins. These dictionaries serve as a look-up table for making subsequent predictions of solvent accessibility of amino acid residues. We find that predictions made in this way are very close to those made using more sophisticated methods of solvent accessibility prediction.

Inter-residue interactions in protein folding and stability.

During the process of protein folding, the amino acid residues along the polypeptide chain interact with each other in a cooperative manner to form the stable native structure. The knowledge about inter-residue interactions in protein structures is very helpful to understand the mechanism of protein folding and stability. In this review, we introduce the classification of inter-residue interactions into short, medium and long range based on a simple geometric approach.

Structural analysis of cation-pi interactions in DNA binding proteins.

Cation-pi interactions play an important role in the stability of protein structures. In this work, we have analyzed the influence of cation-pi interactions in DNA binding proteins. We observed cation-pi interactions in 45 out of 62 DNA binding proteins and there is no significant correlation between the number of amino acid residues and number of cation-pi interactions.

Importance of hydrophobic cluster formation through long-range contacts in the folding transition state of two-state proteins.

Understanding the folding pathways of proteins is a challenging task. The Phi value approach provides a detailed understanding of transition-state structures of folded proteins. In this work, we have computed the hydrophobicity associated with each residue in the folded state of 16 two-state proteins and compared the Phi values of each mutant residue.

ASAView: database and tool for solvent accessibility representation in proteins.

Background: Accessible surface area (ASA) or solvent accessibility of amino acids in a protein has important implications. Knowledge of surface residues helps in locating potential candidates of active sites. Therefore, a method to quickly see the surface residues in a two dimensional model would help to immediately understand the population of amino acid residues on the surface and in the inner core of the proteins.

Locating the stabilizing residues in (alpha/beta)8 barrel proteins based on hydrophobicity, long-range interactions, and sequence conservation.

In nature, 1 out of every 10 proteins has an (alpha/beta)(8) (TIM)-barrel fold, and in most cases, pairwise comparisons show no sequence similarity between them. Hence, delineating the key residues that induce very different sequences to share a common fold is important for understanding the folding and stability of TIM-barrel domains. In this work, we propose a new consensus approach for locating these stabilizing residues based on long-range interactions, hydrophobicity, and conservation of amino acid residues.

Folding mechanism of all-beta globular proteins.

Elucidating the mechanism for the fast folding of proteins is a challenging task. In our earlier work, we introduced the concept of "long-range order" and related it successfully to protein folding rates. In this article, we propose a new hypothesis for the folding of two-state all-beta proteins.

Intermolecular and intramolecular readout mechanisms in protein-DNA recognition.

Protein-DNA recognition plays an essential role in the regulation of gene expression. Regulatory proteins are known to recognize specific DNA sequences directly through atomic contacts (intermolecular readout) and/or indirectly through the conformational properties of the DNA (intramolecular readout). However, little is known about the respective contributions made by these so-called direct and indirect readout mechanisms.

Analysis and prediction of DNA-binding proteins and their binding residues based on composition, sequence and structural information.

Motivation: Though vitally important to cell function, the mechanism of protein-DNA binding has not yet been completely understood. We therefore analysed the relationship between DNA binding and protein sequence composition, solvent accessibility and secondary structure. Using non-redundant databases of transcription factors and protein-DNA complexes, neural network models were developed to utilize the information present in this relationship to predict DNA-binding proteins and their binding residues.

Neural network-based prediction of transmembrane beta-strand segments in outer membrane proteins.

Prediction of transmembrane beta-strands in outer membrane proteins (OMP) is one of the important problems in computational chemistry and biology. In this work, we propose a method based on neural networks for identifying the membrane-spanning beta-strands. We introduce the concept of "residue probability" for assigning residues in transmembrane beta-strand segments.

Role of non-covalent interactions for determining the folding rate of two-state proteins.

Understanding the factors influencing the folding rate of proteins is a challenging problem. In this work, we have analyzed the role of non-covalent interactions for the folding rate of two-state proteins by free-energy approach. We have computed the free-energy terms, hydrophobic, electrostatic, hydrogen-bonding and van der Waals free energies.

ProTherm, version 4.0: thermodynamic database for proteins and mutants.

Release 4.0 of ProTherm, thermodynamic database for proteins and mutants, contains approximately 14,500 numerical data (approximately 450% of the first version) of several thermodynamic parameters along with experimental methods and conditions, and structural, functional and literature information. The sequence and structural information of proteins is connected with thermodynamic data through links between entries in Protein Data Bank, Protein Information Resource and SWISS-PROT and the data in ProTherm.

RVP-net: online prediction of real valued accessible surface area of proteins from single sequences.

Summary: RVP-net is an online program for the prediction of real valued solvent accessibility. All previous methods of accessible surface area (ASA) predictions classify amino acid residues into exposure states and named them buried or exposed based on different thresholds. Real values in some cases were generated by taking the mid points of these state thresholds.

Importance of native-state topology for determining the folding rate of two-state proteins.

Understanding the relationship between amino acid sequences and folding rate of proteins is a challenging task similar to protein folding problem. In this work, we have analyzed the relative importance of protein sequence and structure for predicting the protein folding rates in terms of amino acid properties and contact distances, respectively. We found that the parameters derived with protein sequence (physical-chemical, energetic, and conformational properties of amino acid residues) show very weak correlation (|r| < 0.

Variation of amino acid properties in all-beta globular and outer membrane protein structures.

Discriminating outer membrane (OM) proteins from globular proteins is an important task. The structural analysis of beta-strands dominating globular (all-beta) proteins and OM proteins provides useful insight to distinguish between them. In this work, we analyze the characteristic features of the 20 amino acid residues in all-beta and OM proteins.

Design and training of a neural network for predicting the solvent accessibility of proteins.

A feed-forward neural network has been developed to predict the solvent accessibility/accessible surface area (ASA) of proteins using improved design and training methods. Several network issues ranging from the coding of ASA states to the problem of local minima of learning curve, have been addressed. Successful new approaches to overcome these problems are presented.

Influence of cation-pi interactions in different folding types of membrane proteins.

Cation-pi interactions play an important role to the stability of protein structures. In this work, we analyze the influence of cation-pi interactions in three-dimensional structures of membrane proteins. We found that transmembrane strand (TMS) proteins have more number of cation-pi interactions than transmembrane helical (TMH) proteins.

Role of hydrophobic clusters and long-range contact networks in the folding of (alpha/beta)8 barrel proteins.

Analysis on the three dimensional structures of (alpha/beta)(8) barrel proteins provides ample light to understand the factors that are responsible for directing and maintaining their common fold. In this work, the hydrophobically enriched clusters are identified in 92% of the considered (alpha/beta)(8) barrel proteins. The residue segments with hydrophobic clusters have high thermal stability.

Real value prediction of solvent accessibility from amino acid sequence.

The solvent accessibility of amino acid residues has been predicted in the past by classifying them into exposure states with varying thresholds. This classification provides a wide range of values for the accessible surface area (ASA) within which a residue may fall. Thus far, no attempt has been made to predict real values of ASA from the sequence information without a priori classification into exposure states.

Role of cation-pi interactions to the stability of thermophilic proteins.

Elucidating the factors responsible for exhibiting extreme thermal stability of thermophilic proteins is very important for an understanding of the mechanism of protein stability, as well as to design stable proteins. In this work, we have analyzed the influence of cation-pi interactions to enhance the stability from mesophilic to thermophilic proteins. The favorable residue pairs forming such a system of interactions have been brought out.

Influence of medium- and long-range interactions in different folding types of globular proteins.

Recognition of protein fold from amino acid sequence is a challenging task. The structure and stability of proteins from different fold are mainly dictated by inter-residue interactions. In our earlier work, we have successfully used the medium- and long-range contacts for predicting the protein folding rates, discriminating globular and membrane proteins and for distinguishing protein structural classes.

Important amino acid properties for determining the transition state structures of two-state protein mutants.

Understanding the mechanism in the folding pathways of proteins is an important problem in molecular biology. The Phi-value analysis provides insight into the transition state structures during protein folding. In this work, we have analyzed the relationship between the observed Phi values upon mutations in two-state proteins (FK506 binding protein, chymotrypsin inhibitor and src SH3 domain) and the changes in 48 various physico-chemical, energetic and conformational properties.

Importance of mutant position in Ramachandran plot for predicting protein stability of surface mutations.

Understanding the mechanisms by which mutations affect protein stability is one of the most important problems in molecular biology. In this work, we analyzed the relationship between changes in protein stability caused by surface mutations and changes in 49 physicochemical, energetic, and conformational properties of amino acid residues. We found that the hydration entropy was the major contributor to the stability of surface mutations in helical segments; other properties responsible for size and volume of molecule also correlated significantly with stability.