Enforced Large-Scale Motions in Proteins

"Steered molecular dynamics (SMD) simulations are performed on several model biomolecular systems in order to promote large structural changes in each. External forces are applied to molecular dynamics simulations to promote ligand exit from bacteriorhodopsin, unraveling of titin and fibronectin domains, and rotation of the central stalk within an ATP synthase F1 unit. SMD methods employed include linear constant-velocity extension, multiple-trial segmented path creation, and torque application to enforce angular velocities. The synthesis-direction rotation of ATP synthase central stalk led to: (i) several changes consistent with synthesis nearly 100 A away from the area of torque application, (ii) winding of the coiled-coil stalk, and (iii) a multi-step pathway that allows a key residue (""arginine-finger"" alphaTPArg-373) to enter the ATP binding pocket, thereby inducing catalysis. Spontaneous motions of isolated ATP synthase catalytic subunits are also examined. The subunits, starting from different experimentally observed conformations, perform a combination of twisting and bending motions as they move toward a common conformation, which suggest specific mechanical roles for the subunits in central stalk rotation."

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biophysics and Computational Biology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Isralewitz, Barry

Contributors dc:contributor

• Schulten, Klaus

• Biophysics, General

Language dc:language

eng

Identifier

(MiAaPQ)AAI3301154

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/85463