Seminar: "Massive de novo design of protein fold, function, and dynamics" by Dr. Daniel Silva Manzano
This seminar is open only to the OIST community.
Dr. Daniel Silva Manzano
Biochemistry, Institute for Protein Design
University of Washington (Seattle, WA, USA)
Computational design of de novo proteins holds great promise for developing the next-generation of therapeutic drugs –molecules shaped on demand for treating disease–. I will introduce two recent advances that have just enabled the development of this field. The first, allows massively design and testing thousands of de novo mini-protein binders, and is illustrated by an example where we successfully engineered hundreds of different mini-proteins to neutralize Influenza and Botulinum neurotoxin B. The second breakthrough, allows the design of de novo hyper-stable proteins that mimic the function of natural ones, and is illustrated by the development of a biologically active de novo Interleukin-2 mimetic. At the end of my talk, I will introduce my short-term research plans, which aim to start a new scientific field for the design of intrinsic de novo protein dynamics by combining the state-of-the-art in protein design and multi-scale simulations of protein dynamics. The results of this initiative have the potential to profoundly impact our comprehension of the relation between protein fold and function, and enable a future generation of smart therapeutics, biosensors, and responsive biomaterials.
My principal interest is in the relationship between protein folding, structure and function, and the application of this knowledge for the design of functional de novo proteins. My academic foundation is in Biomedical Research, and since earning my Ph.D. (National Autonomous University of Mexico) I have focused on the computational modeling of proteins. I completed my first postdoctoral research under the supervision of professor Xuhui Huang (Hong Kong University of Science and technology), where I worked in unveiling the long-timescale dynamics of RNA Polymerase II using a combination of Molecular Dynamics Simulations and Markov State Models. During the last five years, I have been a postdoctoral senior fellow at professor David Baker's group (University of Washington, Institute for Protein Design) where my research target has been advancing the state-of-the-art in de novo design of functional proteins. My work involves both the development of novel theoretical/computational frameworks for protein design and its experimental validation.