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Abstract This paper addresses the problem of algorithmic prediction of protein folding pathways, namely, the transient three-dimensional conformations of protein molecules during folding, under constrained rates of entropy change. We formulate the physics-based prediction of folding pathways as a control synthesis problem, where the control inputs guide the protein folding simulations. These folding control inputs are obtained from largescale trust-region subproblems (TRS) utilizing a computationally efficient algorithm with no need for outer iterations. The proposed control synthesis approach, which leverages the solutions obtained from a special generalized eigenvalue problem, avoids potentially cumbersome and unpredictable iterative computations at each protein conformation. Moreover, the TRS-based control inputs align the closed-loop dynamics closely with the kinetostatic compliance method (KCM) reference vector field while satisfying ellipsoidal constraints on the folding control inputs. Finally, we provide conditions for existence and uniqueness of the resulting closed-loop solutions, which are the protein folding pathways under constraints on the rate of entropy change. Numerical simulations utilizing the KCM approach on protein backbones confirm the effectiveness of the proposed framework. 

Considering the non-affine-in-control system governing the motion of a spherical particle trapped inside an optical tweezer, this paper investigates the problem of stabilization of the particle position at the origin through a control Lyapunov function (CLF) framework. The proposed CLF framework enables nonlinear optimization-based closed-loop control of position of tiny beads using optical tweezers and serves as a first step towards design of effective control algorithms for nanomanipulation of biomolecules. After deriving necessary and sufficient conditions for having smooth uniform CLFs for the optical tweezer control system under study, we present a static nonlinear programming problem (NLP) for generation of robustly stabilizing feedback control inputs. Furthermore, the NLP can be solved in real-time with no need for running computationally demanding algorithms. Numerical simulations demonstrate the effectiveness of the proposed control framework in the presence of external disturbances and initial bead positions that are located far away from the laser beam. 

Considering the non-affine-in-control system governing the motion of a spherical particle trapped inside an optical tweezer, this paper investigates the problem of stabilization of the particle position at the origin through a control Lyapunov function (CLF) framework. The proposed CLF framework enables nonlinear optimization-based closed-loop control of position of tiny beads using optical tweezers and serves as a first step towards design of effective control algorithms for nanomanipulation of biomolecules. After deriving necessary and sufficient conditions for having smooth uniform CLFs for the optical tweezer control system under study, we present a static nonlinear programming problem (NLP) for generation of robustly stabilizing feedback control inputs. Furthermore, the NLP can be solved in real-time with no need for running computationally demanding algorithms. Numerical simulations demonstrate the effectiveness of the proposed control framework in the presence of external disturbances and initial bead positions that are located far away from the laser beam. 

This paper investigates the problem of prediction of protein molecule folding pathways under entropy-loss constraints by formulating a control synthesis problem whose solutions are obtained by solving large-scale quadratic programming (QP) optimizations with nonlinear constraints. The utilized non-iterative and computationally efficient algorithm, which is based on solving generalized eigenvalue problems, prevents an unpredictable and potentially large number of iterations at each protein conformation for computing the folding control inputs. The synthesized control inputs remain close to the renowned kinetostatic compliance method (KCM) reference vector field while satisfying proper quadratic inequality constraints that limit the rate of molecule entropy-loss during folding. 

This paper investigates the problem of prediction of protein molecule folding pathways under entropy-loss constraints by formulating a control synthesis problem whose solutions are obtained by solving large-scale quadratic programming (QP) optimizations with nonlinear constraints. The utilized non-iterative and computationally efficient algorithm, which is based on solving generalized eigenvalue problems, prevents an unpredictable and potentially large number of iterations at each protein conformation for computing the folding control inputs. The synthesized control inputs remain close to the renowned kinetostatic compliance method (KCM) reference vector field while satisfying proper quadratic inequality constraints that limit the rate of molecule entropy-loss during folding. 

Understanding the process of protein unfolding plays a crucial role in various applications such as design of folding-based protein engines. Using the well-established kinetostatic compliance (KCM)-based method for modeling of protein conformation dynamics and a recent nonlinear control theoretic approach to KCM-based protein folding, this letter formulates protein unfolding as a destabilizing control analysis/synthesis problem. In light of this formulation, it is shown that the Chetaev instability framework can be used to investigate the KCM-based unfolding dynamics. In particular, a Chetaev function for analysis of unfolding dynamics under the effect of optical tweezers and a class of control Chetaev functions for synthesizing control inputs that elongate protein strands from their folded conformations are presented. Based on the presented control Chetaev function, an unfolding input is derived from the Artstein-Sontag universal formula and the results are compared against optical tweezer-based unfolding.