Marta Enciso Universidad Complutense de Madrid

BIFI Marta Enciso Wylie, JACS, 2009 Kannan, Int. J. Mol. Sci., 2009 Chen, PNAS, 2009 Dobson, Annu. Rev. Biochem., 2006 Protein structure Protein design Folding Aggregation

BIFI Marta Enciso System description Potential definition –Geometrical restrictions –Energy calculation Simulation technique ME & A. Rey, J. Chem. Phys., 2010 Distance Angle

BIFI Marta Enciso Frozen region Meaningful region ME & A. Rey, J. Chem. Phys., 2010 C D B A

BIFI Marta Enciso Domain B of protein A DSSPSTRIDE PyMOLOurs flavodoxin domain B protein A α-spectrin T4 lysozyme fibronectin PDZ domain

BIFI Marta Enciso L. Prieto, D. de Sancho & A. Rey, J. Chem. Phys., 2005 Protein Folding Topology-based models Protein Folding Hydrophobics Hydrogen bonds +

BIFI Marta Enciso *J. Clarke, JMB, 1997 Experiment*4 K Topology-based8 K Topology+HB5 K Peak width Fibronectin type III domain

BIFI Marta Enciso Fibronectin type III domain Two chains

BIFI Marta Enciso A correct description of hydrogen bonds is necessary for understanding protein folding and aggregation We have designed a coarse-grained hydrogen bond model We have proved its validity for obtaining secondary structure elements and detecting real hydrogen bonds It can be successfully applied to the study of protein folding and interprotein interactions

Grupo de Simulación de Proteínas Departamento de Química Física I Universidad Complutense de Madrid Antonio Rey Ramiro Perezzan David de Sancho (U. Cambridge) Lidia Prieto (CUNY) María Larriva (U. Navarra)

Marta Enciso Universidad Complutense de Madrid

BIFI Marta Enciso a)First principles – Quantum Mechanics b)Empiric potentials a)Atomic resolution b)Coarse-grained models a)Others b)Our approach

R1 is a spatial restriction that designates the distance between the two carbons of the hydrogen bonded residues R1 = rij = rj − ri R2 is an orientational restrain which computes the cosine of the angle associated to the relative orientation between the auxiliary vectors of both residues R2 = cos(hi, hj) R3 is also an orientational quantity that computes the cosine of the angle between the direction of the tentative hydrogen bond in the model and each of the auxiliary vectors; thus, R3 is independently calculated for both i and j beads R3i and R3j R3 = cos(hi, rij)