MultiProt — A Multiple Protein Structural Alignment Algorithm

Shatsky, Maxim; Nussinov, Ruth; Wolfson, Haim J.

doi:10.1007/3-540-45784-4_18

Cited by 58 publications

(57 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among these, very few perform both multiple structure comparison and motif detection simultaneously, considering all structures at the same time, rather than initiating from a pairwise superimposed molecular seed, which can lead to a bias. These include MUSTA (29,30), MULTIPROT (34), and MASS (multiple alignment of order-independent secondary structures; O. Dror, H. Bengamini, R.N., and H.W., unpublished data). MUSTA is state of-the-art in its capabilities.…”

Section: Resultsmentioning

confidence: 99%

Protein–protein interactions: Structurally conserved residues distinguish between binding sites and exposed protein surfaces

Elkayam

Wolfson

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

551

500

View full text Add to dashboard Cite

Polar residue hot spots have been observed at protein-protein binding sites. Here we show that hot spots occur predominantly at the interfaces of macromolecular complexes, distinguishing binding sites from the remainder of the surface. Consequently, hot spots can be used to define binding epitopes. We further show a correspondence between energy hot spots and structurally conserved residues. The number of structurally conserved residues, particularly of high ranking energy hot spots, increases with the binding site contact size. This finding may suggest that effectively dispersing hot spots within a large contact area, rather than compactly clustering them, may be a strategy to sustain essential key interactions while still allowing certain protein flexibility at the interface. Thus, most conserved polar residues at the binding interfaces confer rigidity to minimize the entropic cost on binding, whereas surrounding residues form a flexible cushion. Furthermore, our finding that similar residue hot spots occur across different protein families suggests that affinity and specificity are not necessarily coupled: higher affinity does not directly imply greater specificity. Conservation of Trp on the protein surface indicates a highly likely binding site. To a lesser extent, conservation of Phe and Met also imply a binding site. For all three residues, there is a significant conservation in binding sites, whereas there is no conservation on the exposed surface. A hybrid strategy, mapping sequence alignment onto a single structure illustrates the possibility of binding site identification around these three residues.protein-protein interfaces ͉ hot spots ͉ molecular recognition ͉ binding site prediction ͉ residue conservation R inge (1) has raised the question ''what makes a binding site a binding site?'' Many studies have addressed this intriguing and vastly important problem. Being able to a priori predict binding sites would both limit the conformational search in drug design, facilitate the prediction of protein-protein interactions (2), and may provide leads to binding site design.A number of studies have examined the attributes of proteinbinding sites (3-5). Although binding sites on enzyme surfaces typically consist of a concave cleft shape (6, 7) and similarly small ligand binding sites on receptor surfaces (8), this is not the case for the larger protein-protein complexes (9-12). Enzyme-binding sites were shown to frequently be the largest cavities on the enzyme surface (6, 7). On the other hand, the shape of dimer-binding sites is usually quite flat (9) and practically indistinguishable from other patches on the protein surface. Native binding sites do not yield the largest possible interfaces between two protein molecules. A docking study has shown that nonnative interfaces can be larger, and bury a larger extent of total or nonpolar surface areas (13). A similar observation has been made for the number of salt bridges or hydrogen bonds (13,14). Hence, although interfaces are frequently largely hydrophobic ...

show abstract

Section: Resultsmentioning

confidence: 99%

Protein–protein interactions: Structurally conserved residues distinguish between binding sites and exposed protein surfaces

Elkayam

Wolfson

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

551

500

View full text Add to dashboard Cite

show abstract

“…We use very efficient procedure which for small ⑀ produces optimal results. For the details of this procedure see the Appendix in Shatsky et al 25 To enlarge the obtained solutions we apply an iterative improvement procedure as follows. For each solution, after the multiple correspondence between the pivot molecule with the other molecules is established, we apply a rigid transformation that minimizes the RMSD between the matching points.…”

Section: Stage 2 Global Multiple Alignmentmentioning

confidence: 99%

A method for simultaneous alignment of multiple protein structures

Shatsky¹,

Nussinov²,

Wolfson³

2004

Proteins

Self Cite

414

340

View full text Add to dashboard Cite

Here, we present MultiProt, a fully automated highly efficient technique to detect multiple structural alignments of protein structures. MultiProt finds the common geometrical cores between input molecules. To date, most methods for multiple alignment start from the pairwise alignment solutions. This may lead to a small overall alignment. In contrast, our method derives multiple alignments from simultaneous superpositions of input molecules. Further, our method does not require that all input molecules participate in the alignment. Actually, it efficiently detects high scoring partial multiple alignments for all possible number of molecules in the input. To demonstrate the power of MultiProt, we provide a number of case studies. First, we demonstrate known multiple alignments of protein structures to illustrate the performance of MultiProt. Next, we present various biological applications. These include: (1) a partial alignment of hinge-bent domains; (2) identification of functional groups of G-proteins; (3) analysis of binding sites; and (4) protein-protein interface alignment. Some applications preserve the sequence order of the residues in the alignment, whereas others are order-independent. It is their residue sequence order-independence that allows application of MultiProt to derive multiple alignments of binding sites and of protein-protein interfaces, making MultiProt an extremely useful structural tool. Proteins 2004;56:143-156.

show abstract

“…In the past, the structure alignment methods used to identify the same fold in a database were often restricted or biased considering protein structures possessing the same connectivity of secondary structure elements (SSEs) (i.e., a-helices and b-strands) as defined by the polypeptide chain. Only a few methods are available that allow for nonsequential protein structure alignments, for example, MASS (Dror et al 2003), TOPOFIT (Ilyin et al 2004), SCALI (Yuan and Bystroff 2005), and others Weng 2000, 2002;Shatsky et al 2002;Shih and Hwang 2004;Chen et al 2006). Recently, the program GANGSTA (Kolbeck et al 2006) appeared, which ignores the loops connecting different SSEs, like, for example, MASS (Dror et al 2003), PRISM (Yang and Honig 1999), and SARF (Alexandrov and Fischer 1996), and allows nonsequential protein structure alignment.…”

mentioning

confidence: 99%

Novel protein folds and their nonsequential structural analogs

Guerler

Knapp

2008

Protein Science

View full text Add to dashboard Cite

Newly determined protein structures are classified to belong to a new fold, if the structures are sufficiently dissimilar from all other so far known protein structures. To analyze structural similarities of proteins, structure alignment tools are used. We demonstrate that the usage of nonsequential structure alignment tools, which neglect the polypeptide chain connectivity, can yield structure alignments with significant similarities between proteins of known three-dimensional structure and newly determined protein structures that possess a new fold. The recently introduced protein structure alignment tool, GANGSTA, is specialized to perform nonsequential alignments with proper assignment of the secondary structure types by focusing on helices and strands only. In the new version, GANGSTA+, the underlying algorithms were completely redesigned, yielding enhanced quality of structure alignments, offering alignment against a larger database of protein structures, and being more efficient. We applied DaliLite, TM-align, and GANGSTA+ on three protein crystal structures considered to be novel folds. Applying GANGSTA+ to these novel folds, we find proteins in the ASTRAL40 database, which possess significant structural similarities, albeit the alignments are nonsequential and in some cases involve secondary structure elements aligned in reverse orientation. A web server is available at http:// agknapp.chemie.fu-berlin.de/gplus for pairwise alignment, visualization, and database comparison.

show abstract

MultiProt — A Multiple Protein Structural Alignment Algorithm

Cited by 58 publications

References 20 publications

Protein–protein interactions: Structurally conserved residues distinguish between binding sites and exposed protein surfaces

Protein–protein interactions: Structurally conserved residues distinguish between binding sites and exposed protein surfaces

A method for simultaneous alignment of multiple protein structures

Novel protein folds and their nonsequential structural analogs

Contact Info

Product

Resources

About