Hello everyone,
The next speaker of Theochem lectures will be Prof. Eugene Shackhnovich. We
have some spots for both students and postdocs to meet with him on
Thursday, March 24th and some spots for lunch. If you want to meet with him
or/and to attend lunch, please let me know.
Tere
PS. These are the details of his lecture:
Wednesday, March 13th, MIT Building 4, Room 163.
Understanding evolution on multiple scales: from protein physics to
population geneticsBiological phenomena unfold in a broad range of scales
ranging from molecules to cells to populations and ecosystems. Variation of
molecular properties of biomolecules profoundly impact the ability of cells
to survive and propagate (fitness). Finally, the fate of a mutation is
decided by Darwinian selection on the level of the population, where three
outcomes are possible: fixation in the population, elimination by purifying
selection or separation in the population in a subdominant clone
(polymorphism). In this lecture I will outline my lab’s and others efforts
in an emerging new field which merges molecular mechanism with evolution. I
will review basic concepts and models that contributed to our multiscale
understanding of physical-chemical basis of biological phenomena. First, I
will discuss physical chemistry of protein folding. I will present the
fundamental heteropolymer model of protein folding and briefly outline the
statistical mechanical analysis, which uncovered the energy gap criterion -
the necessary and sufficient conditions for a heteropolymer sequence to
encode a foldable protein. I will highlight the analogy and fundamental
differences between heteropolymer and spin glass models. I will also
discuss how understanding of basic principles of protein folding helps in
our efforts to design new proteins and decipher the ‘’messages’’ hidden in
multiple sequence alignment. I will then discuss the analogy between
sequence selection for energy gaps and statistical mechanics of a class of
generalized spin models. The statistical mechanical view of sequence
selection enjoyed renaissance with the development of statistical methods
to derive structural information about proteins from the analysis of
variation in multiple sequence alignment. Finally I will discuss the
relation between selection for foldable sequences and thermodynamic and
kinetic mechanisms of protein folding such as first-order-like
cooperativity. Next, I will present recent efforts at modeling evolutionary
dynamics that merges molecular mechanisms with population genetics.
Traditional population genetics models are agnostic to the
physical-chemical nature of mutational effects. Rather they operate with an
a’priori assumed distributions of fitness effects (DFE) of mutations from
which evolutionary dynamics are derived. Alternatively some population
genetics models aim to derive DFE from evolutionary observations. In
departure with this tradition the novel multiscale models integrate the
molecular effects of mutations on physical properties of proteins into
physically intuitive yet detailed genotype-phenotype relationship (GPR)
assumptions. I will present a range of models from simple analytical
diffusion-based model on biophysical fitness landscapes to more
sophisticated computational models of populations of model cells where
genetic changes are mapped into molecular effects using biophysical
modeling of proteins and ensuing fitness changes determine the fate of
mutations in realistic population dynamics. Examples of insights derived
from biophysics-based multiscale models include the scale-free character of
Protein Universe, the fundamental limit on mutation rates in living
organisms, physics of thermal adaptation, co-evolution of protein
interactions and abundances in cytoplasm and related results, some of which
I will present and discuss. Finally I will briefly present “bottom-up:
experimental efforts based on genome editing approaches to test basic
assumptions of multiscale biophysics-based models of evolution.
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