Computer Simulation Studies of Pattern Recognition in Biomimetic Polymers

Abstract

The overall aim of this research has been to understand the molecular phenomena governing recognition in biological processes such as antibody-antigen binding, transmembrane signaling, viral-inhibition, etc. Specifically, we use computer simulations to study the thermodynamics of recognition of patterns in a copolymer bulk adsorbed on a heterogeneous surfaces, recognition of monomer sequences in copolymers adsorbed on heterogeneous surfaces, and recognition of nucleotide sequences in DNA microarrays.

We first focus on the recognition of a bulk pattern in an AB diblock copolymer film adsorbed on a heterogeneous surface. We investigate how a pattern imposed in a copolymer film at a certain distance from the surface propagates through the film onto an adsorbing heterogeneous surface. We bias the copolymer film to adopt a specified target pattern and then use simulation to design a surface pattern that helps the adsorbed film to maintain that target pattern. We examine the effect of varying the copolymer chain length, the size of the target pattern, and the distance, $z'$, from the surface where the target pattern is applied on the extent of pattern transfer. At constant chain length, pattern transfer is best when the pattern size brings the energy of the system close to the energy when no pattern is applied. At constant pattern size, pattern transfer is best in the systems with longer chains because longer chains are more likely to adsorb as brushes and loops, which then helps transfer the pattern through the adsorbed film down to the surface.

We extend our work to designing heterogeneous surfaces that can recognize and selectively adsorb copolymer sequences. In most of the theoretical work in the area of the pattern recognition by biomimetic polymers the question of how to design optimal surface patterns for recognizing specific monomer sequences in copolymers, has not been answered yet. We have developed a novel simulation method to design surfaces for recognizing specific monomer sequences in copolymers. We fix the sequence statistics of the AB copolymers and adsorb them on a surface containing two types of sites. We allow the simulation to iterate towards an optimal surface pattern that can "recognize" and selectively adsorb the copolymer sequence. For copolymers with less blocky sequences the designed surfaces recognize the correct sequence well when the segment-surface interactions dominate over the intersegment interactions. For copolymers with more blocky sequences recognition is good when the segment-surface interactions are only slightly stronger than the intersegment interactions.

We further extend our study to the recognition of nucleotide sequences in DNA microarrays. DNA microarrays has been widely adopted by the scientific community for a variety of applications. In order to improve performance and to design next generation microarrays there is a need for a fundamental understanding of the interplay between the various factors that affect microarray performance. To gain such an understanding we study the thermodynamics and the kinetics of hybridization of single stranded "target" genes in solution with complementary "probe" DNA molecules immobilized on a microarray surface. Using Monte Carlo simulations and a coarse-grained lattice model we examine how various parameters affect the hybridization process. We observe that as the probe length decreases the specificity increases. Probes with segments that are complementary to the segments at either ends of the target have higher specificity than the probes complementary to the center portion of the target. Analysis of the hybridization kinetics reveals that the segments at the ends of the probe have a high probability of starting the hybridization and the segments towards the center of the probe remain bound to the target for a longer time.