Anatoly B. Kolomeisky - US grants

Anatoly Kolomeisky of Rice University is supported by the Theoretical and Computational Chemistry Program to pursue research and disseminate knowledge in the area of non-equilibrium processes relevant to a microscopic chemistry-based understanding of biology. He will study the dynamics of polymer translocation across nanopores, extend models to explain why the ligand-receptor bond rupture as a function of loading rate deviates from Hooke's law, investigate molecular motors, and determine the mechanisms for polymerization in biologically interesting filaments. This field lies at the interface of chemistry, physics and biology and the research will be closely coupled to the training of undergraduate, graduate and postdoctoral students.

The underlying role of physical chemistry in biology remains an intellectually challenging problem area of great relevance to future biochemical technologies. Problems addressed in this proposal will allow for a better understanding of targeted delivery of pharmaceuticals and subsequent dispersal. A related area in need of a microscopic understanding is how conversion of energy into motion proceeds in biological systems. Examples of such processes, all of which are facilitated by molecular motors, include cell division and transport, molecular contraction and genetic transcription. Kolomeisky plans to extend his research on molecular motors. Imparting the knowledge and requisite skills to a multidisciplinary array of chemical, biological and physical scientists will be accomplished by introducing a course on biophysical chemistry that is aimed at the advanced undergraduate or beginning graduate level student. Early interest in this new area will be raised by outreach to high school students and teachers.

James Tour
The objective of this research is to develop external electronic and optical methods for controllably imaging, sensing, propelling and actuating nanocars and nanotrucks and to devise theoretical models for predicting the motion and output from these diminutive structures. The approach is to synthesize new nanocar entities that are suitable for rolling motion and susceptible to electronic manipulation, imaging using a host of microscopies and devising theoretical models for predicting the mechanisms, range of motion and work output extractable from truly nano-sized single-molecule machines.
Intellectual merit:Transport of goods and materials between points is at the heart of all engineering and construction in real-world systems. As researchers delve into the arena of the nano-sized world, it beckons that they learn to manipulate and transport nanometer-scale materials in a similar manner. This proposed work outlines a method to control the motion of nanocars at the nanoscale level, and thereby pave the way for future bottom-up nanoscale construction.
Broader Impact: The research plan outlined above will be leveraged with education and outreach efforts using the NanoKids program, thereby multiplying this program's impact on grades 6-12 students and teachers, undergraduate students, graduate students, and traditionally underrepresented groups in the sciences and engineering. This uses the attractiveness of nanoscale science to introduce fundamental concepts in chemistry, physics and biology including how those concepts eventually make their way into the marketplace thus impacting everyday life. Funding this work will provide a path to future construction while laying groundwork for education from middle school to post graduate studies.

TECHNICAL SUMMARY
This research project, supported by the Solid State and Materials Chemistry (SSMC) Program in the Division of Materials Research, National Science Foundation aims to study kinetically-controlled syntheses of anisotropic gold nanostructures and their colloidal crystallization in aqueous media. While numerous 3D crystals of spherical particles are known, there are no analogous systems composed of rod-like building blocks. This is because nearly all existing syntheses of nanorods cannot control their length, which often makes them unsuitable for long range 3D crystallization. Seed-mediated synthesis of gold nanorods is a rare example of the reaction producing rods that are fairly well-defined in terms of their length. However, this method is currently non-scalable and cannot offer a sufficient quantity of nanorods to conduct a comprehensive study of their crystallization. This project will develop a route that can scale the synthesis up to four orders of magnitude. The key of the proposed approach is based on uniform amplification of preformed nanorods by reducing residual gold ions on their surface. Preliminary findings show that this goal can be achieved if the rate of reduction is very low, which allows for complete suppression of random nucleation events. Once the large quantities of near-monodisperse nanorods are produced, their crystallization into 3D single crystals will be systematically studied. The project will determine the role of various parameters such as size distribution and purity of rods, their interaction with the underlying substrates, and the rate of solvent evaporation. Of particular importance will be the role of CTAB surfactant that must be present in solution during crystallization. When the best combination of structural and physical variables is identified, periodic arrays of colloidal single crystals will be assembled on lithographically patterned substrates. Measurements of optical, electrical, and mechanical properties of crystals along and perpendicular to the axes of nanorods will be performed in order to assess their direction-dependent vectorial nature.

NON-TECHNICAL SUMMARY
Significant interest in gold nanoparticles with controlled shapes has grown dramatically in the past decade. However, they are often too difficult to make and/or purify. The current commercial price of gold nanorods is more than 7,000 times the price of bulk gold. Therefore, a development of more efficient large-scale synthesis will resolve the issue of their accessibility, which is the main bottleneck of their real-life applications in anticancer therapy, military devices, and invisible cloak technology. Better understanding of mechanisms that govern the assembly of non-spherical particles into large crystals will offer novel types of nanomaterials with direction-dependent properties. The new scientific knowledge generated in the course of this project will be widely disseminated via information sharing techniques and Web2.0 communications. Video materials containing a detailed demonstration of the synthesis of gold nanorods and real-time imaging of 3D crystals by optical and electron microscopy will be posted on the YouTube and Rice University web sites. Of particular importance will be the interactions with science teachers from local middle schools that have a large population of minority students. The PI and his graduate students will use their extensive experience with molecular graphics for 3D visualization of nanostructures and colloidal assemblies in order to create a unique type of activity in Houston public schools that currently collaborate with Rice University. In addition, an exciting outreach activity is planned at the intersection of science and art, which will involve collaborative interactions with the Museum of Fine Arts, Houston.

Anatoly Kolomeisky of Rice University is supported by an award from the Chemical Theory, Models and Computational Methods Program in the Chemistry Division to develop theoretical approaches to understand how proteins and DNA, the most important molecules in all living systems, interact with each other in supporting fundamental processes of life. Analyzing these processes at the molecular level requires novel theoretical and computational tools that are capable of describing the complexity of living systems. The project involves close collaboration with experimental research groups. High school students, undergraduates and graduate students, and postdoctoral associates participate in the research and receive invaluable training in an important and timely field.

The project focuses on developing a fundamental theoretical framework for uncovering microscopic mechanisms of protein search for specific target sites on DNA molecules. The role of various physical and chemical properties of DNA and proteins in these phenomena are tested using a combination of discrete-stochastic models and simulation techniques. The theoretical predictions are tested using single-molecule spectroscopic studies, chemical kinetic experiments and advanced bioinformatics methods. An outreach program developed by Professor Kolomeisky for local high-school students provides the opportunity for them to learn and participate in real scientific work in an academic setting. The broader impacts of this project include a multi-disciplinary training program for young researchers of different levels that will prepare them better for future technological and industrial challenges. In addition, the outreach program promotes advancements in our understanding of cellular processes that may lead to new medical drugs and bio-inspired materials.

Anatoly Kolomeisky of William Marsh Rice University is supported by an award from the Chemical Theory, Models and Computational Methods Program in the Chemistry Division to theoretically investigate interactions between two major classes of biological molecules: DNA and proteins. This project is co-funded by the Molecular Biophysics Program in the Molecular and Cellular Biosciences Division. DNA encodes the genetic plans for all living organisms. Proteins read this information and implement it in the cell. Proper timing is a key aspect of protein-DNA interactions due to the dynamic nature of living cells. If the proper interactions do not occur at the right time, the entire biological system can fail catastrophically. Understanding protein-DNA interactions can lead to new insights for drug discovery and contribute to technological breakthroughs such as bio-inspired or biomimetic materials. Professor Kolomeisky is combining theoretical modeling, simulation, and bioinformatics to understand the molecular foundations of the temporal dependence and efficiency of protein-DNA interactions. Specific questions include: how proteins identify the correct DNA binding sites in performing their functions; the effects of DNA loop formation on multi-site proteins that can bind at different DNA sites; mechanisms of DNA editing using the newly-discovered CRISPR associated protein technology; and understanding the tradeoff between strong binding and fast recognition in determining how proteins bind to DNA. Close collaborations with experimental and theoretical groups will enable testing of the new models, and promote a deeper understanding of these complex natural processes. Professor Kolomeisky is providing opportunities for high school and undergraduate students from underrepresented groups to participate in this research and gain valuable training and experience for their future careers. Outreach activities include a high-school scientific projects competition, co-organization of an undergraduate chemistry research symposium, public lectures delivered at venues such as the Rice Science Café, and continued collaboration with the Rice robotics systems lab to create online games based on the results of this research.

This project focuses on developing a theoretical program to analyze the temporal dependence of protein-DNA interactions. These fundamental interactions are analyzed using a variety of theoretical tools including discrete-state stochastic models, first-passage analysis, bioinformatics methods and extensive Monte Carlo computer simulations. The advantage of this multiscale approach is that it takes into account in a consistent manner the major physical and chemical properties of DNA and proteins interacting in the complex cellular environment. In collaboration with experimental research groups, theoretical predictions are tested using various techniques, including single-molecule spectroscopy, chemical kinetics, and bioinformatic analysis. An outreach program developed by Professor Kolomeisky provides the opportunity for local high-school students and undergraduate students from underrepresented minority groups to participate in scientific research in an academic setting. The project also highlights the benefits of science for society by directly presenting scientific findings to the local community in the informal setting of café discussions, as well as communicating with science writers in local newspapers and participating in scientific Internet blog discussions. The broader impacts of this project include a multidisciplinary training program for young researchers of different levels that will prepare them better for future technological and industrial challenges.