Kino‐Geometric Modeling: Insights into Protein Molecular Mechanisms

Budday D, Leyendecker S, van den Bedem H (2019)

Publication Language: English

Publication Type: Conference contribution, Original article

Publication year: 2019

Journal

Proceedings in Applied Mathematics and Mechanics Gesellschaft für Angewandte Mathematik und Mechanik (GAMM)

Publisher: Proceedings in Applied Mathematics and Mechanics (PAMM)

Book Volume: 19

Conference Proceedings Title: Proc. Appl. Math. Mech (PAMM)

Event location: Vienna

DOI: 10.1002/pamm.201900448

Open Access Link: https://onlinelibrary.wiley.com/doi/abs/10.1002/pamm.201900448

Abstract

Proteins are dynamic macromolecules that perform an immense variety of biological functions on a broad range of spatio‐temporal scales. Their conformational ensemble is a fundamental determinant of functionality in health and disease. While computational advances have increasingly enabled the computation of atomically detailed trajectories from Molecular Dynamics (MD) simulations, there remain considerable drawbacks when aiming for fast, yet elaborate insights into the molecular mechanisms of function. Here, we explore the potential of kinematics and geometry based methods, inspired from traditional robotics, to study protein conformational dynamics. Using geometric tools, we demonstrate insights into molecular mobility from instantaneous rigidity and flexibility analysis on selected example systems. Resulting motions from kinematically sampling along collective degrees of freedom show qualitative and quantitative agreement with motions from MD simulations. Coupled to sophisticated motion planning strategies, our approach is capable of providing structural ensemble representations from sparse experimental data such as double electron‐electron resonance (DEER) that remain difficult to interpret otherwise. Overall, we establish our Kino‐Geometric Sampling tool KGS as an efficient alternative to obtain high‐level insights into molecular mechanisms across scales, with ample applications in protein design and human health.

Authors with CRIS profile

Dominik Budday Institute of Applied Dynamics Sigrid Leyendecker Institute of Applied Dynamics

Involved external institutions

Stanford University

United States (USA) (US)

How to cite

APA:

Budday, D., Leyendecker, S., & van den Bedem, H. (2019). Kino‐Geometric Modeling: Insights into Protein Molecular Mechanisms. In Proc. Appl. Math. Mech (PAMM). Vienna, AT: Proceedings in Applied Mathematics and Mechanics (PAMM).

MLA:

Budday, Dominik, Sigrid Leyendecker, and Henry van den Bedem. "Kino‐Geometric Modeling: Insights into Protein Molecular Mechanisms." Proceedings of the GAMM Annual Meeting, Vienna Proceedings in Applied Mathematics and Mechanics (PAMM), 2019.

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