A framework for computational and experimental methods: identifying dimerization residues in CCR chemokine receptors.
Solving relevant biological problems requires answering complex questions. Addressing such questions traditionally implied the design of time-consuming experimental procedures which most of the time are not accessible to average-sized laboratories. The current trend is to move towards a multidisciplinary approach integrating both theoretical knowledge and experimental work. This combination creates a powerful tool for shedding light on biological problems. To illustrate this concept, we present here a descriptive example of where computational methods were shown to be a key aspect in detecting crucial players in an important biological problem: the dimerization of chemokine receptors. Using evolutionary based sequence analysis in combination with structural predictions two CCR5 residues were selected as important for dimerization and further validated experimentally. The experimental validation of computational procedures demonstrated here provides a wealth of valuable information not obtainable by any of the individual approaches alone.
de Juan
David
D
Protein Design Group, National Center of Biotechnology (CNB-CSIC) Cantoblanco, Madrid, Spain.
Mellado
Mario
M
Rodríguez-Frade
José Miguel
JM
Hernanz-Falcón
Patricia
P
Serrano
Antonio
A
del Sol
Antonio
A
Valencia
Alfonso
A
Martínez-A
Carlos
C
Rojas
Ana María
AM
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry* / Q000276:immunology; D001665:Binding Sites; D019281:Dimerization; D008956:Models, Chemical; D018448:Models, Immunological; D008969:Molecular Sequence Data; D011485:Protein Binding; D019713:Receptors, CCR5 / Q000737:chemistry* / Q000276:immunology; D020539:Sequence Analysis, Protein / Q000379:methods*
D000596:Amino Acids; D019713:Receptors, CCR5