Large Language Models (LLMs) can be used as repositories of biological and chemical information to generate pharmacological lead compounds. However, for LLMs to focus on specific drug targets typically requires experimentation with progressively more refined prompts. Results thus become dependent not just on what is known about the target, but also on what is known about the prompt- engineering. In this paper, we separate the prompt into domain-constraints that can be written in a standard logical form and a simple text-based query. We investigate whether LLMs can be guided, not by refining prompts manually, but by refining the logical component automatically, keeping the query unchanged. We describe an iterative procedure LMLF (“Language Model with Logical Feedback”) in which the constraints are progressively refined using a logical notion of generalisation. On any iteration, newly generated instances are verified against the constraint, providing "logical-feedback" for the next iteration's refinement of the constraints. We evaluate LMLF using two well-known  targets (inhibition of the Janus Kinase 2; and Dopamine Receptor D2); and two different LLMs (GPT-3 and PaLM). We show that LMLF, starting with the same logical constraints and query text, can be used to guide both LLMs to generate potential leads. We find: (a)  Binding affinities of LMLF-generated molecules are skewed towards higher binding affinities than those from existing baselines; (b) LMLF results in generating molecules that are skewed towards higher binding affinities than without logical feedback; (c) Assessment by a computational chemist suggests that LMLF generated compounds may be novel inhibitors. These findings suggest that LLMs with logical feedback may provide a mechanism for generating new leads without requiring the domain-specialist to acquire sophisticated skills in prompt-engineering.

Generating Novel Leads for Drug Discovery Using LLMs with Logical Feedback

Main track - Applications

technical paper

We are pleased to announce the Thirty-Eighth AAAI Conference on Artificial Intelligence (AAAI-24), which will be held in Vancouver, British Columbia at the Vancouver Convention Centre – West Building from 20-27 February, 2024.

The purpose of the AAAI conference series is to promote research in Artificial Intelligence (AI) and foster scientific exchange between researchers, practitioners, scientists, students, and engineers across the entirety of AI and its affiliated disciplines. AAAI-24 will feature technical paper presentations, special tracks, invited speakers, workshops, tutorials, poster sessions, senior member presentations, competitions, and exhibit programs, and a range of other activities to be announced.

We expect for AAAI-24 to be an in-person conference – one author of all accepted papers will be expected to present work in person unless there are exceptional circumstances that prevent this.<br><br><br><br>

In order to access the AAAI-24 event page you need to register [here](https://aaai.org/aaai-conference/registration/)

AAAI 2024

The purpose of the AAAI conference series is to promote research in Artificial Intelligence (AI) and foster scientific exchange between researchers, practitioners, scientists, students, and engineers across the entirety of AI and its affiliated disciplines. 

Shreyas Bhat Brahmavar

1

1

SHORT BIO

Presentations

Generating Novel Leads for Drug Discovery Using LLMs with Logical Feedback

Stay up to date with the latest Underline news!

PRESENTATIONS

CONFERENCES

COMPANY

RESOURCES