Can we predict photochemistry?
The newly born field of photoreaction discovery aims to predict the outcome of photon absorption without assuming any prior knowledge of the molecule's photoactivity, a hard problem in chemistry. For this purpose, it is necessary to methodically map ground and excited state potential energy surfaces.
The Nonadiabatic Nanoreactor extensively samples the intersection seam between electronic states to find accessible conical intersection types, and systematically connects them to available photoproducts.
We want to expand the capabilities of this computational tool and leverage existing techniques such as nonadiabatic molecular dynamics to streamline the high-throughput screening of tens of molecules and proteins.
Can we artificially improve fluorescence?
Fluorescent probes in bio-imaging serve as light bulbs to study the anatomy and function of live tissues. However, engineering proteins to fluoresce with the desired experimental brightness and color is not trivial. Biliproteins can be engineered to fluoresce in the far red or near infrared portion of the light spectrum, an important property for deep imaging.
While natural bilin chromophores present great features, we can learn how to tune their chemical and photochemical properties using theory. This can directly translate to improvements in membrane permeability, fluorescence quantum yield, and absorption/emission wavelength.
Our goal is to understand the atomistic details of the excited state behavior of natural bilins and use such information to alchemically design new molecules with tunable properties, eventually embedding them inside protein scaffolds to build a new library of bio-imaging tools.
Can we design better photoactive proteins?
We envision two main directions for the engineering of biliproteins: we can try to either enhance its fluorescence properties for bio-imaging purposes, or gain control of its possible photochromism to develop novel optogenetics tools.
From a computational standpoint, this translates into assessing the propensity of the chromophore to undergo radiative decay vs. photoisomerization.
Our group seeks to gain insights into the working mechanism of biliproteins and use this information to strategically insert point mutations and find or create knobs to tune the function of biliproteins.
Our approach is based on systematic and high-throughput mutant creation and screening. We aim at producing large datasets for data analysis (e.g., ML, causal inference) and deriving rational design principles for optogenetics and bio-imaging agents.