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Patricia Theodosopoulos

Publications and source records attributed to Patricia Theodosopoulos.

3 recordsLinked to original sources

Robustness and Evolvability of the B Cell Mutator Mechanism

We present a model that considers the maturation of the antibody population following primary antigen presentation as a global optimization problem. The trade-off that emerges from our model describes the balance between the safety of mutations that lead to local improvements in affinity and the necessity of the system to undergo global reconfigurations in the antibody's shape in order to achieve its goals, in this example of fast-paced evolution. The parameter p which quantifies this trade-off appears to be itself both robust and evolvable. This parallels the rapidity and consistency of the optimization operating during the biologic response. In this paper, we explore the robust qualities and evolvability of this tunable control parameter, p.

q-bio.QM

Evolution at the Edge of Chaos: A Paradigm for the Maturation of the Humoral Immune Response

We study the maturation of the antibody population following primary antigen presentation as a global optimization problem. Emphasis is placed on the trade-off between the safety of mutations that lead to local improvements to the antibody's affinity and the necessity of eventual mutations that result in global reconfigurations in the antibody's shape. The model described herein gives evidence of the underlying optimization process from which the rapidity and consistency of the biologic response could be derived.

q-bio.QM

A computational study of the statistical mechanics of antibody-antigen conformations

We describe the representation of the chemical affinity between the antigen-combining site of the immunoglobulin molecule and the antigen molecule as the probability of the two molecules existing in a bound state. Our model is based on the identification of shape attractors in the configuration space for the joint antibody / antigen combining site sequence. We parameterize configuration space in terms of Ramachandran angles. The shape attractors allow us to construct a Markov chain whose steady state distribution gives rise to the desired attachment probability. As a result we are able to delineate the enthalpic, entropic and kinetic components of affinity and study their interactions.

q-bio.QM