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Dynamical Redesign of Biomolecular Networks

Objetivo

Enzymes created by Nature are still more selective and can be orders of magnitude more efficient than man-made catalysts, in spite of recent advances in the design of de novo catalysts and in enzyme redesign. The optimal engineering of either small molecular or of complex biological catalysts requires both (i) accurate quantitative computational methods capable of a priori assessing catalytic efficiency, and (ii) molecular design principles and corresponding algorithms to achieve, understand and control biomolecular catalytic function and mechanisms. Presently, the computational design of biocatalysts is challenging due to the need for accurate yet computationally-intensive quantum mechanical calculations of bond formation and cleavage, as well as to the requirement for proper statistical sampling over very many degrees of freedom. Pioneering enhanced sampling and analysis methods have been developed to address crucial challenges bridging the gap between the available simulation length and the biologically relevant timescales. However, biased simulations do not generally permit the direct calculation of kinetic information. Recently, I and others pioneered simulation tools that can enable not only accurate calculations of free energies, but also of the intrinsic molecular kinetics and the underlying reaction mechanisms as well. I propose to develop more robust, automatic, and system-tailored sampling algorithms that are optimal in each case. I will use our kinetics-based methods to develop a novel theoretical framework to address catalytic efficiency and to establish molecular design principles to key design problems for new bio-inspired nanocatalysts, and to identify and characterize small molecule modulators of enzyme activity. This is a highly interdisciplinary project that will enable fundamental advances in molecular simulations and will unveil the physical principles that will lead to design and control of catalysis with Nature-like efficiency.

Régimen de financiación

ERC-STG - Starting Grant

Institución de acogida

UNIVERSITY COLLEGE LONDON
Aportación neta de la UEn
€ 968 817,50
Dirección
Gower Street
WC1E 6BT London
United Kingdom

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Región
London Inner London — West Camden and City of London
Tipo de actividad
Higher or Secondary Education Establishments
Otras fuentes de financiación
€ 968 817,50

Beneficiarios (2)

UNIVERSITY COLLEGE LONDON
United Kingdom
Aportación neta de la UEn
€ 968 817,50
Dirección
Gower Street
WC1E 6BT London

Ver en el mapa

Región
London Inner London — West Camden and City of London
Tipo de actividad
Higher or Secondary Education Establishments
Otras fuentes de financiación
€ 968 817,50
KING'S COLLEGE LONDON
United Kingdom
Aportación neta de la UEn
€ 531 181,50
Dirección
Strand
WC2R 2LS London

Ver en el mapa

Región
London Inner London — West Westminster
Tipo de actividad
Higher or Secondary Education Establishments
Otras fuentes de financiación
€ 531 181,50