title: Comparative protein structure modeling by combining multiple templates and optimizing sequence-to-structure alignments.
abstract: BACKGROUND
  Two major bottlenecks in advancing comparative protein structure modeling are the efficient combination of multiple template structures and the generation of a correct input target-template alignment.
  
  
  RESULTS
  A novel method, Multiple Mapping Method with Multiple Templates (M4T) is introduced that implements an algorithm to automatically select and combine Multiple Template structures (MT) and an alignment optimization protocol (Multiple Mapping Method, MMM). The MT module of M4T selects and combines multiple template structures through an iterative clustering approach that takes into account the 'unique' contribution of each template, their sequence similarity among themselves and to the target sequence, and their experimental resolution. MMM is a sequence-to-structure alignment method that optimally combines alternatively aligned regions according to their fit in the structural environment of the template structure. The resulting M4T alignment is used as input to a comparative modeling module. The performance of M4T has been benchmarked on CASP6 comparative modeling target sequences and on a larger independent test set, and showed favorable performance to current state of the art methods.
authors.affiliation: Department of Biochemistry and Seaver Center for Bioinformatics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Narcis
authors.initials: N
authors.lastname: Fernandez-Fuentes
authors.forename: Brajesh K
authors.initials: BK
authors.lastname: Rai
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Madrid-Aliste
authors.forename: J Eduardo
authors.initials: JE
authors.lastname: Fajardo
authors.forename: András
authors.initials: A
authors.lastname: Fiser
mesh_terms: D000465:Algorithms; D016000:Cluster Analysis; D003198:Computer Simulation; D008956:Models, Chemical; D008958:Models, Molecular; D010363:Pattern Recognition, Automated / Q000379:methods*; D011506:Proteins / Q000737:chemistry* / Q000648:ultrastructure; D016415:Sequence Alignment / Q000379:methods*; D020539:Sequence Analysis, Protein / Q000379:methods*; D017386:Sequence Homology, Amino Acid