Design principle of Protein’s Mechanical Resistance

1. Design principle of Protein’s Mechanical Resistance Investigator: Hui Lu, Ph.D., Bioengineering, Collaborators: Julio Fernandez (Columbia University), Hongbin Li (U of British Columbia) • Mechanical signals play key role in physiological processes by controlling protein conformational changes • Uncover design principles of mechanical protein stability • Relationship between protein structure and mechanical response; Deterministic design of proteins • Atomic level of understanding is needed from biological understanding and protein design principles • All-atom computational simulation for protein conformational changes – Steered Molecular Dynamics • Free energy reconstruction from non-equilibrium protein unfolding trajectories • Force partition calculation for mechanical load analysis • Modeling solvent-protein interactions for different molecules • Coarse-grained model with Molecular dynamics and Monte Carlo simulations • Identified key force-bearing patch that controlled the mechanical stability of proteins. • Discovered a novel pathway switch mechanism for tuning protein mechanical properties. • Calculated how different solvent affect protein’s mechanical resistance. • Goal: Computationally design protein molecules with specific mechanical properties for bio-signaling and bio-materials.

2. Atomic & Molecular BioNanotechnology G.AliMansoori, Bio & Chem Eng Depts Prime Grant Support: ARO, KU, UMSL, ANL • Diamondoids and Gold Nanoparticle - based nanobiotechnology - Applications for Drug Delivery. • Quantum and statistical mechanics of small systems - Development of ab initio models and equations of state of nanosystems. Phase transitions, fragmentations. • Molecular dynamics simulation of nano systems - Non-extensivity and internal pressure anomaly. • DNA-Dendrimersnano-cluster formation. • Nanoparticles-Protein Attachment • Nano-Imaging (AFM & STM), Microelectrophoresis • Ab Initio computations (Applications of Gaussian 98) • Nano-Systems Simulations (Molecular Dynamics) • Nano-Thermodynamics and Statistical Mechanics • DNA-DendrimerNano-Cluster Electrostatics (CTNS, 2005) • Nonextensivity and Nonintensivity in Nanosystems - A Molecular Dynamics SumulationJ Comput & TheortNanoscience (CTNS,2005) • Principles of Nanotechnology (Book) World Scientific Pub. Co (2005) • Statistical Mechanical Modeling and its Application to NanosystemsHandbook of Theor & ComputNanoscience and Nanotechnology (2005) • Phase-Transition and Fragmentation in Nano-Confined Fluids J Comput & TheortNanoscience (2005). • Interatomic Potential Models for Nanostructures" EncyclNanoscience & Nanotechnology (2004).

3. Integrating Nanostructures with Biological Structures Investigators: M. Stroscio, ECE and BioE; M. Dutta, ECE Prime Grant Support: ARO, NSF, AFOSR, SRC, DARPA, DHS • Coupling manmade nanostructures with biological structures to monitor and control biological processes. • For underlying concepts see Biological Nanostructures and Applications of Nanostructures in Biology: Electrical, Mechanical, & Optical Properties, edited by Michael A. Stroscio and MitraDutta (Kluwer, New York, 2004). • Synthesis of nanostructures • Binding nanostructures to manmade structures • Modeling electrical, optical and mechanical properties of nanostructures • Experimental characterization of integrated manmade nanostructure-biological structures • Numerous manmade nanostructures have been functionalized with biomolecules • Nanostructure-biomolecule complexes have been used to study a variety of biological structures including cells • Interactions between nanostructures with biomolecules and with biological environments have been modeled for a wide variety of systems • Ultimate goal is controlling biological systems at the nanoscale